Tag Archives: COVID-19

Adverse cardiac events following mRNA COVID-19 vaccination

Pharmaceutical Science, , , , ,

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 76-100, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1524_11.1.76

Review

Adverse cardiac events following mRNA COVID-19 vaccination: A systematic review and meta-analysis

[Eventos cardíacos adversos tras la vacunación con COVID-19 ARNm: Una revisión sistemática y metaanálisis]

Eka Arum Cahyaning Putri1*, Misbakhul Munir1, Hayuris Kinandita Setiawan1, Lilik Herawati1, Gadis Meinar Sari1, Citrawati Dyah Kencono Wungu1, Hendri Susilo2,3, Henry Sutanto4

1Department of Medical Physiology and Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

2Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Department of Cardiology and Vascular Medicine, Universitas Airlangga Hospital, Surabaya, Indonesia.

4Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University, 6211 Maastricht, The Netherlands.

*E-mail: eka-arum-cp@fk.unair.ac.id

Abstract

Context: Although have been proven able to control the prevalence of coronavirus disease-19 (COVID-19), Pfizer-BioNTech and Moderna COVID-19 vaccines are reported to have possible side effects on the heart.

Aims: To know the magnitude of adverse events in the cardiac after messenger ribonucleic acid (mRNA)-based vaccination.

Methods: An electronic search in PubMed, Web of Science, Scopus, and Ebsco/Cinahl was performed. The keywords were: “COVID-19 vaccine”, “SARS-CoV-2 vaccine”, “myocarditis”, “myopericarditis”, “pericarditis”, “myocardial infarction”, and “myocardial injury”. The electronic search was updated until March 2022. STATA/MP Statistical Software: Release 14 (StataCorp LLC, College Station, Texas) was used in this study to perform a meta-analysis of a random-effect for myocarditis, pericarditis, myocarditis, myocardial infarction, and myocardial injury.

Results: Twenty-one case reports/case series studies with a total of 62 individuals who had been vaccinated against COVID-19 mRNA (Pfizer-BioNTech and Moderna) were included in the systematic review. Whereas seven observational cohort studies had 170,053,333 people who had been vaccinated, 245 of whom had myocarditis. In addition, two observational cohort studies with 13,948,595 vaccinated individuals, 16 of whom developed pericarditis. There was only one observational cohort study that had a total of 7,183,889 people who had been vaccinated and 11 had myopericarditis. Based on the pooled incidence, the result is <0.002%.

Conclusions: The Pfizer-BioNTech and Moderna vaccines have a low incidence of myocarditis. Men are more likely to develop post-COVID-19 myocarditis with an average age of 22 years and in the age range of 21-40 years. The type of mRNA COVID-19 vaccine that causes myocarditis the most is Pfizer. The diagnosis of myocarditis is mostly made by troponin examination. COVID-19 mRNA vaccination has a low incidence of myocarditis.

Keywords: cardiac disease; cardiac events; COVID-19; mRNA vaccines; SARS-CoV-2.

Resumen

Contexto: Aunque se ha demostrado que pueden controlar la prevalencia de la enfermedad por coronavirus-19 (COVID-19), se ha informado que las vacunas contra COVID-19 de Pfizer-BioNTech y Moderna tienen posibles efectos secundarios sobre el corazón.

Objetivos: Conocer la magnitud de los efectos adversos en el corazón tras la vacunación basada en ácido ribonucleico mensajero (ARNm).

Métodos: Se realizó una búsqueda electrónica en PubMed, Web of Science, Scopus y Ebsco/Cinahl. Las palabras clave fueron: “vacuna COVID-19”, “vacuna SARS-CoV-2”, “miocarditis”, “miopericarditis”, “pericarditis”, “infarto de miocardio” y “lesión miocárdica”. La búsqueda electrónica se actualizó hasta marzo de 2022. Software estadístico STATA/MP: Versión 14 (StataCorp LLC, College Station, Texas) se utilizó en este estudio para realizar un metanálisis de efecto aleatorio para miocarditis, pericarditis, miocarditis, infarto de miocardio y lesión miocárdica.

Resultados: Se incluyeron en la revisión sistemática 21 estudios de informes de casos/series de casos con un total de 62 individuos que habían sido vacunados contra COVID-19 ARNm (Pfizer-BioNTech y Moderna). Mientras que siete estudios observacionales de cohortes contaban con 170.053.333 personas que habían sido vacunadas, 245 de las cuales presentaron miocarditis. Además, dos estudios observacionales de cohortes con 13.948.595 personas vacunadas, 16 de las cuales desarrollaron pericarditis. Sólo hubo un estudio observacional de cohortes con un total de 7.183.889 personas vacunadas y 11 tuvieron miopericarditis. Basándose en la incidencia agrupada, el resultado es <0,002%.

Conclusiones: Las vacunas Pfizer-BioNTech y Moderna tienen una baja incidencia de miocarditis. Los hombres son más propensos a desarrollar miocarditis post-COVID-19 con una edad media de 22 años y en el rango de edad de 21-40 años. El tipo de vacuna COVID-19 de ARNm que causa más miocarditis es Pfizer. El diagnóstico de la miocarditis se realiza principalmente mediante el examen de troponina. La vacunación con ARNm COVID-19 tiene una baja incidencia de miocarditis.

Palabras Clave: enfermedad cardiaca; eventos cardiacos; COVID-19; vacunas de ARNm; SARS-CoV-2.

Download the PDF file .

 
Citation Format: Putri EAC, Munir M, Setiawan HK, Herawati L, Sari GM, Wungu CDK, Susilo H, Sutanto H (2023) Adverse cardiac events following mRNA COVID-19 vaccination: A systematic review and meta-analysis. J Pharm Pharmacogn Res 11(1): 76–100. https://doi.org/10.56499/jppres22.1524_11.1.76
References

Ammirati E, Cipriani M, Moro C, Raineri C, Pini D, Sormani P, Mantovani R, Varrenti M, Pedrotti P, Conca C, Mafrici A, Grosu A, Briguglia D, Guglielmetto S, Perego GB, Colombo S, Caico SI, Giannattasio C, Maestroni A, Carubelli V, Metra M, Lombardi C, Campodonico J, Agostoni P, Peretto G, Scelsi L, Turco A, Di Tano G, Campana C, Belloni A, Morandi F, Mortara A, Cirò A, Senni M, Gavazzi A, Frigerio M, Oliva F, Camici PG; Registro Lombardo delle Miocarditi (2018) Clinical presentation and outcome in a contemporary cohort of patients with acute myocarditis: Multicenter Lombardy Registry. Circulation 138(11): 1088–1099. https://doi.org/10.1161/CIRCULATIONAHA.118.035319

Ammirati E, Frigerio M, Adler E, Basso C, Birnie D, Brambatti M (2020) Management of acute myocarditis and chronic inflammatory cardiomyopathy: An expert consensus document. Circ Heart Fail 13(11): e007405. https://doi.org/10.1161/CIRCHEARTFAILURE.120.007405

Anzini M, Merlo M, Sabbadini G, Barbati G, Finocchiaro G, Pinamonti B, Salvi A, Perkan A, Di Lenarda A, Bussani R, Bartunek J, Sinagra G (2013) Long-term evolution and prognostic stratification of biopsy-proven active myocarditis. Circ Res 128: 2384–2394. https://doi.org/10.1161/CIRCULATIONAHA.113.003092

 Aquaro GD, Perfetti M, Camastra G, Monti L, Dellegrottaglie S, Moro C, Pepe A, Todiere G, Lanzillo C, Scatteia A, Di Roma M, Pontone G, Perazzolo Marra M, Barison A, Di Bella G (2017) Cardiac magnetic resonance working group of the Italian Society of Cardiology. Cardiac MR with late gadolinium enhancement in acute myocarditis with preserved systolic function: ITAMY study. J Am Coll Cardiol 70: 1977–1987. https://doi.org/10.1016/j.jacc.2017.08.044

Aromataris E, Munn Z (Editors) (2020) JBI Manual for Evidence Synthesis. JBI. https://doi.org/10.46658/JBIMES-20-01

Arvin AM, Fink K, Schmid MA, Cathcart A, Spreafico R, Havenar-Daughton C, Lanzavecchia A, Corti D, Virgin HW (2020) A perspective on potential antibody-dependent enhancement of SARS-CoV-2. Nature 584: 353–363. https://doi.org/10.1038/s41586-020-2538-8

Barda N, Dagan N, Ben-Shlomo Y, Kepten E, Waxman J, Ohana R, Hernán MA, Lipsitch M, Kohane I, Netzer D, Reis BY, Balicer RD (2021) Safety of the BNT162b2 mRNA COVID-19 vaccine in a nationwide setting. New Engl J Med 385(12): 1078–1090. https://doi.org/10.1056/NEJMoa2110475

Bartok E, Hartmann G (2020) Immune sensing mechanisms that discriminate self from altered self and foreign nucleic acids. Immunity 53: 54–77. https://doi.org/10.1016/j.immuni.2020.06.014

Bass A, Patterson JH, Adams KF Jr (2010) Perspective on the clinical application of troponin in heart failure and states of cardiac injury. Heart Fail Rev 15(4): 305–317. https://doi.org/10.1007/s10741-008-9124-8

Biesbroek PS, Beek AM, Germans T, Niessen HW, van Rossum AC (2015) Diagnosis of myocarditis: Current state and future perspectives. Int J Cardiol 191: 211–219. https://doi.org/10.1016/j.ijcard.2015.05.008

Bleier J, Vorderwinkler KP, Falkensammer J, Mair P, Dapunt O, Puschendorf B, Mair J (1998) Different intracellular compartmentations of cardiac troponins and myosin heavy chains: a causal connection to their different early release after myocardial damage. Clin Chem 44: 1912–1918.

Boehmer TK, Kompaniyets L, Lavery AM, Hsu J, Ko JY, Yusuf H, Romano SD, Gundlapalli AV, Oster ME, Harris AM (2021) Association between COVID-19 and myocarditis using hospital-based administrative data – United States, March 2020-January 2021. MMWR Morb Mortal Wkly Rep 70(35): 1228–1232. http://dx.doi.org/10.15585/mmwr.mm7035e5

Buttà C, Zappia L, Laterra G, Roberto M (2020) Diagnostic and prognostic role of electrocardiogram in acute myocarditis: A comprehensive review. Ann Noninvasive Electrocardiol 25(3): e12726. https://doi.org/10.1111/anec.12726

Caforio AL, Calabrese F, Angelini A, Tona F, Vinci A, Bottaro S, Ramondo A, Carturan E, Iliceto S, Thiene G, Daliento L (2007) A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis. Eur Heart J 28(11): 1326–1333. https://doi.org/10.1093/eurheartj/ehm076

Cai C, Peng Y, Shen E, Huang Q, Chen Y, Liu P, Guo C, Feng Z, Gao L, Zhang X, Gao Y, Liu Y, Han Y, Zeng S, Shen H (2021) A comprehensive analysis of the efficacy and safety of COVID-19 vaccines. Mol Ther 29(9): 2794–2805. https://doi.org/10.1016/j.ymthe.2021.08.001

CDC (2021a) Centres for Diseases Control and Prevention (CDC). Local Reactions, Systemic Reactions, Adverse Events, and Serious Adverse Events: Moderna COVID-19 Vaccine. https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/reactogenicity.html [Consulted: 7 February 2022].

CDC (2021b) Centres for Diseases Control and Prevention (CDC). Reactions and Adverse Events of the Pfizer-BioNTech COVID-19 Vaccine. Available online: https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/reactogenicity.html [Consulted: 7 February 2022].

CDC (2021c) Centres for Diseases Control and Prevention (CDC). Multisystem Inflammatory Syndrome (MIS). Atlanta, ga: us department of health and human services. https://www.cdc.gov/mis/index.html [Consulted: 20 March 2022].

Cheng MP, Kozoriz MG, Ahmadi AA, Kelsall J, Paquette K, Onrot JM (2016) Post-vaccination myositis and myocarditis in a previously healthy male. Allergy Asthma Clin Immunol 12: 6. https://doi.org/10.1186/s13223-016-0114-4

Cereda A, Conca C, Barbieri L, Ferrante G, Tumminello G, Lucreziotti S, Guazzi M, Mafrici A (2021) Acute myocarditis after the second dose of SARS-CoV-2 vaccine: Serendipity or atypical causal relationship? Anatol J Cardiol 25(7): 522–523. https://doi.org/10.5152/AnatolJCardiol.2021.99

Crowley A, Ackerman M (2019) Mind the gap: How interspecies variability in igg and its receptors may complicate comparisons of human and non-human primate effector function. Front Immunol 10: 697. https://doi.org/10.3389/fimmu.2019.00697

Deb A, Abdelmalek J, Iwuji K, Nugent K (2021) Acute myocardial injury following COVID-19 vaccination: a case report and review of current evidence from vaccine adverse events reporting system database. J Prim Care Community Health 12: 21501327211029230. https://doi.org/10.1177/21501327211029230

Dekkers G, Bentlage AEH, Stegmann TC, Howie HL, Lissenberg-Thunnissen S, Zimring J, Rispens T, Vidarsson G (2017) Affinity of human IgG subclasses to mouse Fc gamma receptors. MAbs 9(5): 767–773. https://doi.org/10.1080/19420862.2017.1323159  

di Dedda EA, Barison A, Aquaro GD, Ismail TF, Hua A, Mantini C, Ricci F, Pontone G, Volpe A, Secchi F, Di Renzi P, Lovato L, Niro F, Liguori C, De Biase C, Monti L, Cirò A, Marano R, Natale L, Moliterno E, Esposito A, Vignale D, Faletti R, Gatti M, Porcu M, Saba L, Chimenti C, Galea N, Francone M (2022) Cardiac magnetic resonance imaging of myocarditis and pericarditis following COVID-19 vaccination: a multicenter collection of 27 cases. Eur Radiol 32(7): 4352–4360. https://doi.org/10.1007/s00330-022-08566-0

Dickey JB, Albert E, Badr M, Laraja KM, Sena LM, Gerson DS, Saucedo JE, Qureshi W, Aurigemma GP (2021) A series of patients with myocarditis following SARS-CoV-2 vaccination with mRNA-1279 and BNT162b2. JACC: Cardiovasc Imaging 14(9): 1862–1863. https://doi.org/10.1016/j.jcmg.2021.06.003

Dye C, Mills MC (2021) COVID-19 vaccination passports. Science 371(6535): 1184. https://doi.org/10.1126/science.abi5245

Ehrlich P, Klingel K, Ohlmann-Knafo S Hüttinger S, Sood  N, Pickuth D, Kindermann M (2021) Biopsy-proven lymphocytic myocarditis following first mRNA COVID-19 vaccination in a 40-year-old male: case report. Clin Res Cardiol 110(11): 1855–1859. https://doi.org/10.1007/s00392-021-01936-6

Fairweather D, Cooper LT Jr, Blauwet LA (2013) Sex and gender differences in myocarditis and dilated cardiomyopathy. Curr Probl Cardiol 38(1): 7–46. https://doi.org/10.1016/j.cpcardiol.2012.07.003

Feng S, Chiu SS, Chan ELY, Kwan MYW, Wong JSC, Leung CW, Chung Lau Y, Sullivan SG, Malik Peiris JS, Cowling BJ (2018) Effectiveness of influenza vaccination on influenza-associated hospitalizations over time among children in Hong Kong: a test-negative case-control study. Lancet Respir Med 6(12): 925–934. https://doi.org/10.1016/s2213-2600(18)30419-3

Ferdinands JM, Gaglani M, Martin ET, Monto AS, Middleton D, Silveira F, Talbot HK, Zimmerman R, Patel M (2021) Waning vaccine effectiveness against influenza-associated hospitalizations among adults, 2015-2016 to 2018-2019, United States hospitalized adult influenza vaccine effectiveness network. Clin Infect Dis 73(4): 726–729. https://doi.org/10.1093/cid/ciab045

Fischinger S, Boudreau CM, Butler AL, Streeck H, Alter G (2019) Sex differences in vaccine-induced humoral immunity. Semin Immunopathol 41(2): 239–249. https://doi.org/10.1007/s00281-018-0726-5

Frisancho-Kiss S, Coronado MJ, Frisancho JA, Lau VM, Rose NR, Klein SL, Fairweather D (2009) Gonadectomy of male BALB/c mice increases Tim-3(+) alternatively activated M2 macrophages, Tim-3(+) T cells, Th2 cells and Treg in the heart during acute coxsackievirus-induced myocarditis. Brain Behav Immun 23(5): 649–657. https://doi.org/10.1016/j.bbi.2008.12.002

Gargano JW, Wallace M, Hadler SC, Langley G, Su JR, Oster ME, Broder KR, Gee J, Weintraub E, Shimabukuro T, Scobie HM, Moulia D, Markowitz LE, Wharton M, McNally VV, Romero JR, Talbot HK, Lee GM, Daley MF, Oliver SE (2021) Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the advisory committee on immunization practices – united states, June 2021. MMWR Morb Mortal Wkly Rep 70(27): 977–982. http://dx.doi.org/10.15585/mmwr.mm7027e2

Guo CW, Alexander M, Dib Y, Lau PKH, Weppler AM, Au-Yeung G, Lee B, Khoo C, Mooney D, Joshi SB, Creati L, Sandhu S (2020) A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies. Eur J Cancer 124: 15–24. https://doi.org/10.1016/j.ejca.2019.09.009

Gürdoğan M, Yalta K (2020) Myocarditis associated with immune checkpoint inhibitors: Practical considerations in diagnosis and management. Anatol J Cardiol 24(2): 68–75. https://doi.org/10.14744/anatoljcardiol.2020.79584

Hasnie AA, Hasnie UA, Patel N, Aziz MU, Xie M, Lloyd SG, Prabhu SD (2021) Perimyocarditis following first dose of the mRNA-1273 SARS-CoV-2 (Moderna) vaccine in a healthy young male: a case report. BMC Cardiovasc Disord 21: 375. https://doi.org/10.1186/s12872-021-02183-3

Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savović J, Schulz KF, Weeks L, Sterne JAC (2011) The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ (Online) 343(7829): 1–9. https://doi.org/10.1136/bmj.d5928

Hudson B, Mantooth R, DeLaney M (2021) Myocarditis and pericarditis after vaccination for COVID-19. JACEP Open 2: e12498. https://doi.org/10.1002/emp2.12498

Imazio M, Angelico G, Andriani M, Lobetti-Bodoni L, Davini O, Giustetto C, Rinaldi M (2018) Prevalence and prognostic impact of septal late gadolinium enhancement in acute myocarditis with or without preserved left ventricular function. Am J Cardiol 122(11): 1955–1958. https://doi.org/10.1016/j.amjcard.2018.08.038

Imazio M, Brucato A, Barbieri A, Ferroni F, Maestroni S, Ligabue G, Chinaglia A, Cumetti D, Della Casa G, Bonomi F, Mantovani F, Di Corato P, Lugli R, Faletti R, Leuzzi S, Bonamini R, Modena MG, Belli R (2013) Good prognosis for pericarditis with and without myocardial involvement: Results from a multicenter, prospective cohort study. Circulation 128(1): 42–49. https://doi.org/10.1161/CIRCULATIONAHA.113.001531

Imazio M, Brucato A, Spodick D, Adler Y (2014) Prognosis of myopericarditis as determined from previously published reports. J Cardiovasc Med (Hagerstown) 15: 835–839. https://doi.org/10.2459/jcm.0000000000000082

Jackson N, Kester K, Casimiro D, Gurunathan S, DeRosa F (2020) The promise of mRNA vaccines: A biotech and industrial perspective. NPJ Vaccines 5: 11. https://doi.org/10.1038/s41541-020-0159-8

Jensen S, Thomsen A (2012) Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion. J Virol 86: 2900–2910. https://doi.org/10.1128/jvi.05738-11

June Choe Y, Yi S, Hwang I, Kim J, Park YJ, Cho E, Jo M, Lee H, Hwa Choi E (2022) Safety and effectiveness of BNT162b2 mRNA COVID-19 vaccine in adolescents. Vaccine 40(5): 691–694. https://doi.org/10.1016/j.vaccine.2021.12.044

Kim HW, Jenista ER, Wendell DC, Azevedo CF, Campbell MJ, Darty SN, Parker MA, Kim RJ (2021) Patients with acute myocarditis following mRNA COVID-19 vaccination. JAMA Cardiol 6(10): 1196–1201. https://doi.org/10.1001/jamacardio.2021.2828

Kim IC, Kim H, Lee HJ, Kim JY, Kim JY (2021) Cardiac imaging of acute myocarditis following COVID-19 mRNA vaccination. J Korean Med Sci 36(32): e229. https://doi.org/10.3346/jkms.2021.36.e229

King WW, Petersen MR, Matar RM, Budweg JB, Cuervo Pardo L, Petersen JW (2021) Myocarditis following mRNA vaccination against SARS-CoV-2, a case series. Am Heart J Plus: Cardiol Res Pract 8: 100042. https://doi.org/10.1016/j.ahjo.2021.100042

Klugar M, Riad A, Mekhemar M, Conrad J, Buchbender M, Howaldt HP, Attia S (2021) Side effects of mRNA-based and viral vector-based COVID-19 vaccines among german healthcare workers. Biology 10(8): 752. https://doi.org/10.3390/biology10080752

Knowlton KU, Knight S, Muhlestein JB, Le VT, Horne BD, May HT, Stenehjem E, Anderson JL (2021) A small but significant increased incidence of acute pericarditis identified after vaccination for SARS-COV-2. Circulation 144(Suppl. 1): A11396. https://doi.org/10.1161/circ.144.suppl_1.11396

Lasrado N, Reddy J (2020) An overview of the immune mechanisms of viral myocarditis. Rev Med Virol 30: e2131. https://doi.org/10.1002/rmv.2131

Lyden D, Olszewski J, Feran M, Job L, Huber S (1987) Coxsackievirus B-3-induced myocarditis. Effect of sex steroids on viremia and infectivity of cardiocytes. Am J Pathol 126: 432–438.

Maron BJ, Udelson JE, Bonow RO, Nishimura RA, Ackerman MJ, Estes NAM, Cooper LT, Link MS, Maron MS (2015) Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis. Circulation 132(22): e273–e280. https://doi.org/10.1161/CIR.0000000000000239

Marshall M, Ferguson ID, Lewis P, Jaggi P, Gagliardo C, Collins JS, Shaughnessy R,  Caron R, Fuss C, Corbin KJE, Emuren L, Faherty E, Hall EK, Pentima CD, Oster ME, Paintsil E, Siddiqui S, Timchak DM, Guzman-Cottrill JA (2021) Symptomatic acute myocarditis in 7 adolescents after Pfizer-BioNTech COVID-19 vaccination. Pediatrics 148(3): e2021052478. https://doi.org/10.1542/peds.2021-052478

Matta A, Kunadharaju R, Osman M (2021) Clinical presentation and outcomes of myocarditis post mRNA vaccination: a meta-analysis and systematic review. Cureus 11: e19240. https://doi.org/10.7759/cureus.19240

McLean K, Johnson TJ (2021) Myopericarditis in a previously healthy adolescent male following COVID-19 vaccination: A case report. Acad Emerg Med 28(8): 918–921. https://doi.org/10.1111/acem.14322

Mevorach D, Anis E, Cedar N, Bromberg M, Haas EJ, Nadir E, Olsha-Castell S, Arad D, Hasin T, Levi N, Asleh R, Amir O, Meir K, Cohen D, Dichtiar R, Novick D, Hershkovitz Y, Dagan R, Leitersdorf I, Ben-Ami R, Miskin I, Saliba W, Muhsen K, Levi Y, Green MS, Keinan-Boker L, Alroy-Preis S (2021) Myocarditis after BNT162b2 mRNA vaccine against COVID-19 in Israel. N Engl J Med  385(23): 2140–2149. https://doi.org/10.1056/nejmoa2109730  

Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA, Group PP (2015) Preferred reporting items for systematic review and meta-analysis protocols (Prisma-p) 2015 statement. Syst Rev 4(1): 1. https://doi.org/doi:10.1186/2046-4053-4-1

Montgomery J, Ryan M, Engler R, Hoffman D, McClenathan B, Collins L, Loran D, Hrncir D, Herring K, Platzer M, Adams N, Sanou A, Cooper LT (2021) Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military. JAMA Cardiol 6(10): 1202–1206. https://doi.org/10.1001/jamacardio.2021.2833

Nassar M, Nso N, Gonzalez C, Lakhdar S, Alshamam M, Elshafey M, Abdalazeem Y, Nyein A, Punzalan B, Durrance RJ, Alfishawy M, Bakshi S, Rizzo V (2021) COVID-19 vaccine-induced myocarditis: Case report with literature review. Diabetes Metab Syndr 15(5): 102205. https://doi.org/10.1016/j.dsx.2021.102205

Nevet A (2021) Acute myocarditis associated with anti-COVID-19 vaccination. Clin Exp Vaccine Res 10(2): 196–197. https://doi.org/10.7774/cevr.2021.10.2.196

Oster ME, Shay DK, Su JR, Gee J, Creech CB, Broder KR, Edwards K, Soslow JH, Dendy JM, Schlaudecker E, Lang SM, Barnett ED, Ruberg FL, Smith MJ, Campbell MJ, Lopes RD, Sperling LS, Baumblatt JA, Thompson DL, Marquez PL, Strid P, Woo J, Pugsley R, Reagan-Steiner S, DeStefano F, Shimabukuro TT (2022) Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to august 2021. JAMA 327(4): 331–340. https://doi.org/doi:10.1001/jama.2021.24110

Pardi N, Hogan M, Porter F, Weissman D (2018) mRNA vaccines – a new era in vaccinology. Nat Rev Drug Discov 17: 261–279. https://doi.org/10.1038/nrd.2017.243

Park JW, Lagniton PNP, Liu Y, Xu RH (2021) mRNA vaccines for COVID-19: What, why and how. Int J Biol Sci 17(6): 1446–1460. https://doi.org/10.7150/ijbs.59233

Patel YR, Louis DW, Atalay M. Agarwal S, Shah NR (2021) Cardiovascular magnetic resonance findings in young adult patients with acute myocarditis following mRNA COVID-19 vaccination: a case series. J Cardiovasc Magn Reson 23: 101. https://doi.org/10.1186/s12968-021-00795-4

Patone M, Mei XW, Handunnetthi L, Dixon S, Zaccardi F, Shankar-Hari M, Watkinson P, Khunti K, Harnden A, Coupland CAC, Channon KM, Mills NL, Sheikh A, Hippisley-Cox J (2022) Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19  vaccination or SARS-CoV-2 infection. Nat Med 28(2): 410–422. https://doi.org/10.1038/s41591-021-01630-0

Pilishvili T, Fleming-Dutra KE, Farrar JL, Gierke R, Mohr NM, Talan DA, Krishnadasan A, Harland KK, Smithline HA, Hou PC, Lee LC, Lim SC, Moran GJ, Krebs E, Steele M, Beiser DG, Faine B, Haran JP, Nandi U, Schrading WA, Chinnock B, Henning DJ, Vecchio FL, Nadle J, Barter D, Brackney M, Britton A, Marceaux-Galli K, Lim S, Phipps EC, Dumyati G, Pierce R, Markus TM, Anderson DJ, Debes AK, Lin M, Mayer J, Babcock HM, Safdar N, Fischer M, Singleton R, Chea N, Magill SS, Verani J, Schrag S (2021) Interim estimates of vaccine effectiveness of Pfizer-BioNTech and Moderna COVID-19  vaccines among health care personnel – 33 US sites, January-March 2021. MMWR. Morb Mortal Wkly Rep 70(20): 753–758. https://doi.org/10.15585/mmwr.mm7020e2

Potluri T, Fink A, Sylvia K, Dhakal S, Vermillion MS, Steeg LV,  Deshpande S, Narasimhan H, Klein SL (2019) Associated changes in the impact of sex steroids on influenza vaccine responses in males and females. NPJ Vaccines 4: 29. https://doi.org/10.1038/s41541-019-0124-6

Rombey T, Doni K, Hoffmann F, Pieper D, Allers K (2020) More systematic reviews were registered in PROSPERO each year, but few records’ status was up-to-date. J Clin Epidemiol 117: 60–67. https://doi.org/10.1016/j.jclinepi.2019.09.026

Rosner CM, Genovese L, Tehrani BN, Atkins M, Bakhshi H, Chaudhri S, Damluji AA, Lemos JAD, Desai SS, Emaminia A, Flanagan MC, Khera A, Maghsoudi A, Mekonnen G, Muthukumar A, Saeed IM, Sherwood MW, Sinha SS, O’Connor CM, deFilippi CR (2021) Myocarditis temporally associated with COVID-19 vaccination. Circulation 144(6): 502–505. https://doi.org/10.1161/CIRCULATIONAHA.121.055891

Rowland C, Johnson CY (2020) Even finding a COVID-19 vaccine won’t be enough to end the pandemic. Washington Post. May 11, 2020. https://www.washingtonpost.com/business/2020/05/11/coronavirus-vaccine-global-supply/ [Consulted: 1 February 2022].

Ruggieri A, Anticoli S, D’Ambrosio A, Giordani L, Viora M (2016) The influence of sex and gender on immunity, infection and vaccination. Ann Ist Super Sanita 52(2): 198–204. https://doi.org/10.4415/ann_16_02_11

Sahin U, Kariko K, Tureci O (2014) mRNA-based therapeutics–developing a new class of drugs. Nat Rev Drug Discov 13: 759–780. https://doi.org/10.1038/nrd4278

Salah HM, Mehta JL (2021) COVID-19 vaccine and myocarditis. Am J Cardiol 157: 146–148. https://doi.org/10.1016/j.amjcard.2021.07.009

Shaw KE, Cavalcante JL, Han BK, Gössl M (2021) Possible association between COVID-19 vaccine and myocarditis: Clinical and CMR findings. JACC: Cardiovascular Imaging 14(9): 1856–1861. https://doi.org/10.1016/j.jcmg.2021.06.002

Shiyovich A, Witberg G, Aviv Y, Eisen A, Orvin K, Wiessman M, Grinberg T, Porter A, Kornowski R, Hamdan A (2021) Myocarditis following COVID-19 vaccination: magnetic resonance imaging study. Eur Heart J Cardiovasc Imaging 3(8): 1075–1082. https://doi.org/10.1093/ehjci/jeab230

Simone A, Herald J, Chen A, Gulati N, Shen AYJ, Lewin B, Lee MS (2021) Acute myocarditis following COVID-19 mRNA vaccination in adults aged 18 years or  older. JAMA Intern Med 181(12): 1668–1670. https://doi.org/10.1001/jamainternmed.2021.5511

Singh B, Kaur P, Cedeno L, Brahimi T, Patel P, Virk H, Shamoon F, Bikkina M (2021) COVID-10 mRNA vaccine and myocarditis. Eur J Case Rep Intern Med 14;8(7): 002681. https://doi.org/10.12890/2021_002681

Singh VP, Pir MS, Buch T, Kaur A, Kela K, Shah P, Miller J, Naseer R, Ghosh P (2021) Myocarditis linked to Pfizer-Biontech COVID-19 vaccine. Chest 160(4): A444. https://doi.org/10.1016/j.chest.2021.07.437

Snapiri O, Danziger CR, Shirman N, Weissbach A, Lowenthal A, Ayalon I, Adam D, Yarden-Bilavsky H, Bilavsky E (2021) Transient cardiac injury in adolescents receiving the BNT162b2 mRNA COVID-19 vaccine. Pediatr Infect Dis J 40(10): e360–e363. https://doi.org/10.1097/INF.0000000000003235

Starekova J, Bluemke DA, Bradham WS, Grist TM, Schiebler ML, Reeder SB (2021) Myocarditis associated with mRNA COVID-19 vaccination. Radiology 301(2): E409–E411. https://doi.org/10.1148/radiol.2021211430

Sung JG, Sobieszczyk PS, Bhatt DL (2021) Acute myocardial infarction within 24 hours after COVID-19 vaccination. Am J Cardiol 156: 129–131. https://doi.org/10.1016/j.amjcard.2021.06.047

Tenforde M, Olson S, Self W, Network IVY, Investigators H (2021) Effectiveness of Pfizer-BioNTech and Moderna vaccines against COVID-19 among hospitalized adults aged ≥65 years—United States, January–March 2021. Morb Mortal Wkly Rep 70: 674–679. https://doi.org/10.15585/mmwr. mm7018e1

Thevathasan T, Kenny MA, Schreiber F, Fairweather D, Cooper LT, Last J, Krause FJJ, Paul J, Poller WC, Skurk C, Landmesser U, Balzer F, Heidecker B (2021) The strongest sex difference in myocarditis prevalence occurred in young adult patients – A descriptive, multi-center cohort study in 7,031 patients over 22 years. Circulation 144(Suppl. 1): A11548–A11548. https://doi.org/10.1161/circ.144.suppl_1.11548  

Thompson M, Burgess J, Naleway A, Tyner H, Yoon S, Meece J, Olsho L, Caban-Martinez A, Fowlkes A, Lutrick K, Groom H, Dunnigan K, Odean M, Hegmann K, Stefanski E, Edwards L, Schaefer-Solle N, Grant L, Ellingson K, Kuntz J, Zunie T, Thiese M, Ivacic L, Wesley M, Mayo Lamberte J, Sun X, Smith M, Phillips A, Groover K, Yoo Y, Gerald J, Brown R, Herring M, Joseph G, Beitel S, Morrill T, Mak J, Rivers P, Poe B, Lynch B, Zhou Y, Zhang J, Kelleher A, Li Y, Dickerson M, Hanson E, Guenther K, Tong S, Bateman A, Reisdorf E, Barnes J, Azziz-Baumgartner E, Hunt D, Arvay M, Kutty P, Fry A, Gaglani M (2021) Prevention and attenuation of COVID-19 with the BNT162b2 and mRNA-1273 vaccines. N Engl J Med 385: 320–329. https://doi.org/10.1056/NEJMoa2107058  

Trachtenberg BH, Hare JM (2017) Inflammatory cardiomyopathic syndromes. Circ Res 121: 803–818. https://doi.org/10.1161/CIRCRESAHA.117.310221

Trigunaite A, Dimo J, Jørgensen TN (2015) Suppressive effects of androgens on the immune system. Cell Immunol 294(2): 87–94. https://doi.org/10.1016/j.cellimm.2015.02.004

Vaccines and Related Biological Products Advisory Committee Meeting (2020) FDA briefing document: Pfizer-BioNTech COVID-19 Vaccine. New York (NY): Pfizer and BioNTech.

Valbuena-López S, Hinojar R, Puntmann VO (2016) Cardiovascular magnetic resonance in cardiology practice: A concise guide to image acquisition and clinical interpretation. Rev Esp Cardiol 69(2): 202–210. https://doi.org/10.1016/j.rec.2015.11.011

Verma AK, Lavine KJ, Lin CY (2021) Myocarditis after Covid-19 mRNA vaccination. N Engl J Med 385: 1332–1334. https://doi.org/10.1056/NEJMc2109975 

Vollmann D, Eiffert H, Schuster A (2021) Acute perimyocarditis following first dose of mRNA vaccine against COVID-19. Dtsch Arztebl Int 118: 546. https://doi.org/10.3238/arztebl.m2021.0288

WHO (2020a) World Health Organization. Statement on the second meeting of the international health. Regulations (2005) emergency committee regarding the outbreak of novel coronavirus. https://www.who.int/news-room/detail/30-01-2020-st [Consulted: 1 February 2022].

WHO (2020b) World Health Organization. COVID-19 Dashboard. In Available online: https://covid19.who.int/ [Consulted: 7 February 2022].

Witberg G, Barda N, Hoss S, Richter I, Wiessman M, Aviv Y, Grinberg T, Auster O, Dagan N, Balicer RD, Kornowski R (2021) Myocarditis after COVID-19 Vaccination in a Large Health Care Organization. N Engl Med 385: 2132–2139. https://doi.org/10.1056/NEJMoa2110737

Wittrup A, Lieberman J (2015) Knocking down disease: a progress report on siRNA therapeutics. Nat Rev Genet 16(9): 543–552. https://doi.org/10.1038/nrg3978

Woudstra L, Juffermans LJM, Rossum VAC (2018) Infectious myocarditis: The role of the cardiac vasculature. Heart Fail Rev 23: 583–595. https://doi.org/10.1007/s10741-018-9688-x

Yap J, Tham MY, Poh J, Toh D, Chan CL, Lim TW, Lim SL, Chia YW, Lim YT, Choo J, Ding ZP, Foo LL, Kuo S, Lau YH, Lee A, Yeo KK (2022) Pericarditis and myocarditis after COVID-19 mRNA vaccination in a nationwide  setting. Ann Acad Med Singap 51(2): 96–100. https://doi.org/10.47102/annals-acadmedsg.2021425

Zachary M, Edoardo A, Catalin T (2019) The development of software to support multiple systematic review types. Int J Evid Based Healthc 17(1): 36–43. https://doi.org/10.1097/XEB.0000000000000152

Zhang L, Awadalla M, Mahmood SS, Nohria A, Hassan MZO, Thuny F, Zlotoff DA, Murphy SP, Stone JR, Golden DLA, Alvi RM, Rokicki A, Jones-O’Connor M, Cohen JV, Heinzerling LM, Mulligan C, Armanious M, Barac A, Forrestal BJ, Sullivan RJ, Kwong RY, Yang EH, Damrongwatanasuk R, Chen CL, Gupta D, Kirchberger MC, Moslehi JJ, Coelho-Filho OR, Ganatra S, Rizvi MA, Sahni G, Tocchetti CG, Mercurio V, Mahmoudi M, Lawrence DP, Reynolds KL, Weinsaft JW, Baksi AJ, Ederhy S, Groarke JD, Lyon AR, Fradley MG, Thavendiranathan P, Neilan TG (2020b) Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis. Eur Heart J 41(18): 1733–1743. https://doi.org/10.1093/eurheartj/ehaa051

Zhang NN, Li XF, Deng YQ, Zhao H, Huang YJ, Yang G, Huang WJ, Gao P, Zhou C, Zhang RR, Guo Y, Sun SH, Fan H, Zu SL, Chen Q, He Q, Cao TS, Huang XY, Qiu HY, Nie JH, Jiang Y, Yan HY, Ye Q, Zhong X, Xue XL, Zha ZY, Zhou D, Yang X, Wang, YC, Ying B, Qi CF (2020a) A thermostable mRNA vaccine against COVID-19. Cell 182(5): 1271–1283.e16. https://doi.org/10.1016/j.cell.2020.07.024

© 2023 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Oxidative stress in COVID-19 infection

Pharmaceutical Science, , , , ,

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 63-75, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1535_11.1.63

Original Article

Oxidative stress in diverse clinical conditions of SARS-CoV-2 Cuban hospitalized patients

[Estrés oxidativo en diferentes condiciones clínicas de pacientes cubanos hospitalizados con SARS-CoV-2]

Lizette Gil-del Valle1*, Rosario Gravier-Hernández1, Mario M. Delgado-Guerra2, Joniel A. Sánchez-Márquez2, Olga E. López-Fernández2, Miguel A. Acosta-Suárez1, Teresa Rosell-Guerra1, Rodolfo Suárez-Iznaga3, Raiza Martínez-Casanueva3, Zullyt Zamora-Rodriguez4, Lidia A. Fernández-García4, Yusimit Bermudez-Alfonso1, María C. Hernández-Gonzalez-Abreu1, Gabino Garrido5**

1Institute “Pedro Kourí” (IPK), Havana, Cuba.

2Hospital Ernesto Guevara, University of Informatics’ Science, Havana, Cuba.

3Hospital Salvador Allende, Havana, Cuba.

4National Center of Scientific Research, BioCubaFarma, Havana, Cuba.

5Departamento de Ciencias Farmacéuticas, Facultad de Ciencias, Universidad Católica del Norte, Antofagasta, Chile.

*E-mail: *lgil@ipk.sld.cu, **gabino.garrido@ucn.cl

Abstract

Context: COVID-19 related to SARS-CoV-2 infection generates inflammation with increased reactive oxygen species production. Drug treatment and others factors could influence systemic oxidative stress during pathogenic insult.

Aims: To determine the redox status in COVID-19 patients with different clinical conditions and explore the relationship between redox and hematological hemochemical variables.

Methods: In this comparative longitudinal study, blood samples were drawn from 160 individuals divided into four groups: COVID-19 asymptomatic, COVID-19 symptomatic (low and moderate symptoms), COVID-19 convalescent, and presumable healthy subjects. Demographic, redox, hematological, and hemochemical indices were assessed. Statistical analyses compared the median values of each variable and explored individual, simultaneous indices, and multivariate alteration.

Results: Relative to the healthy group, acute COVID-19, and convalescent groups had significant differences in global damage indices and antioxidant status (p<0.05). The convalescent group showed significantly higher damage (malondialdehyde, advanced oxidation protein products, nitric oxide) and lower antioxidant enzymatic activities and glutathione concentration compared to other groups (p<0.05). Global modification of redox indices showed that more than 80% of studied individuals in acute conditions had simultaneous detrimental differences compared to a healthy status. The discriminant analysis permitted obtaining two canonical functions (p< 0.05) that reflect 98% of redox variables with 95% of variances with successful case classifications.

Conclusions: These results corroborate that oxidative stress occurred in different COVID-19 and post-acute conditions with different molecular alterations of redox indices. Redox diagnosis should be considered in early diagnosis and treatment of infection, which would be worthwhile to conduct a more comprehensive study and management of disease evolution.

Keywords: antioxidant status; COVID-19; oxidative stress; oxidative damage; SARS-CoV-2.

Resumen

Contexto: El COVID-19 relacionado con la infección por SARS-CoV-2 genera inflamación con aumento de la producción de especies reactivas del oxígeno. El tratamiento farmacológico y otros factores podrían influir en el estrés oxidativo sistémico durante el insulto patogénico.

Objetivos: Determinar el estado redox en pacientes con COVID-19 con diferentes condiciones clínicas y explorar la relación entre las variables redox y hemoquímicas.

Métodos: En este estudio longitudinal comparativo, se extrajeron muestras de sangre de 160 individuos divididos en cuatro grupos: COVID-19 asintomáticos, COVID-19 sintomáticos (síntomas bajos y moderados), COVID-19 convalecientes y sujetos presuntamente sanos. Se evaluaron los índices demográficos, redox, hematológicos y hemoquímicos. Los análisis estadísticos compararon los valores medios de cada variable y exploraron las alteraciones en los índices individuales, simultáneos y multivariadas.

Resultados: En relación con el grupo sano, los grupos COVID-19 agudo y convaleciente presentaron diferencias significativas en los índices de daño global y en el estado antioxidante (p<0,05). El grupo convaleciente mostró un daño significativamente mayor (malondialdehído, productos proteicos de oxidación avanzada, óxido nítrico) y menores actividades enzimáticas antioxidantes y concentración de glutatión en comparación con los otros grupos (p<0,05). La modificación global de los índices redox mostró que más del 80% de los individuos estudiados tenían diferencias perjudiciales simultáneas en comparación con el estado saludable. El análisis discriminante permitió obtener dos funciones canónicas (p< 0,05) que reflejan el 98% de las variables redox con el 95% de las varianzas con clasificaciones de casos acertadas.

Conclusiones: Estos resultados corroboran que el estrés oxidativo se presentó en diferentes COVID-19 y condiciones post-agudas con diferentes alteraciones moleculares de los índices redox. El diagnóstico redox debe ser considerado en el diagnóstico y tratamiento precoz de la infección, lo que valdría la pena para realizar un estudio y manejo más exhaustivo de la evolución de la enfermedad.

Palabras Clave: daño oxidativo; COVID-19; estado antioxidante; estrés oxidativo; SARS-CoV-2.

Download the PDF file .

 
Citation Format: Gil-del Valle L, Gravier-Hernández R, Delgado-Guerra MM, Sánchez-Márquez JA, López-Fernández OE, Acosta-Suárez MA, Rosell-Guerra T, Suárez-Iznaga R, Martínez-Casanueva R, Zamora-Rodriguez Z, Fernández-García LA, Bermudez-Alfonso Y, Hernández-Gonzalez-Abreu MC, Garrido G (2023) Oxidative stress in diverse clinical conditions of SARS-CoV-2 Cuban hospitalized patients. J Pharm Pharmacogn Res 11(1): 63–75. https://doi.org/10.56499/jppres22.1535_11.1.63
References

Ahmed SM, Luo L, Namani A, Wang XJ, Tang X (2017) Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis 1863(2): 585–597. https://doi.org/10.1016/j.bbadis.2016.11.005

Amatore D, Sgarbanti R, Aquilano K, Baldelli S, Limongi D, Civitelli L, Nencioni L, Garaci E, Ciriolo MR, Palamara AT (2015) Influenza virus replication in lung epithelial cells depends on redox-sensitive pathways activated by NOX4-derived ROS. Cell Microbiol 17(1): 131–45. https://doi.org/10.1111/cmi.12343

Azkur AK, Akdis M, Azkur D, Sokolowska M, van de Veen W, Brüggen MC, O’Mahony L, Gao Y, Nadeau K, Akdis CA (2020) Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19. Allergy 75(7): 1564–1581. https://doi.org/10.1111/all.14364

Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL (2009) Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem 390(3): 191–214. https://doi.org/10.1515/BC.2009.033

Bhaskar S, Sinha A, Banach M, Mittoo S, Weissert R, Kass JS, Rajagopal S, Pai AR, Kutty S (2020) Cytokine storm in COVID-19-immunopathological mechanisms, clinical considerations, and therapeutic approaches: The REPROGRAM Consortium position paper. Front Immunol 11: 1648. https://doi.org/10.3389/fimmu.2020.01648

Cecchini R, Cecchini AL (2020) SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression. Med Hypotheses 143: 110102. https://doi.org/10.1016/j.mehy.2020.110102

Ceriello A, Testa R (2009) Antioxidant anti-inflammatory treatment in type 2 diabetes. Diabetes Care 32 Suppl 2(Suppl 2): S232–S236. https://doi.org/10.2337/dc09-S316

Channappanavar R, Perlman S (2017) Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 39(5): 529–539. https://doi.org/10.1007/s00281-017-0629-x

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L (2020a) Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 395(10223): 507–513. https://doi.org/10.1016/S0140-6736(20)30211-7

Chen R, Sang L, Jiang M, Yang Z, Jia N, Fu W, Xie J, Guan W, Liang W, Ni Z, Hu Y, Liu L, Shan H, Lei C, Peng Y, Wei L, Liu Y, Hu Y, Peng P, Wang J, Liu J, Chen Z, Li G, Zheng Z, Qiu S, Luo J, Ye C, Zhu S, Zheng J, Zhang N, Li Y, He J, Li J, Li S, Zhong N; Medical Treatment Expert Group for COVID-19 (2020b) Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China. J Allergy Clin Immunol 146(1): 89–100. https://doi.org/10.1016/j.jaci.2020.05.003

Chiscano-Camón L, Ruiz-Rodriguez JC, Ruiz-Sanmartin A, Roca O, Ferrer R (2020) Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome. Crit Care 24(1): 522. https://doi.org/10.1186/s13054-020-03249-y

Clairborne A (1986) Catalase activity. In: Green-Wald R, editor. Handbook of Methods for Oxygen Radical Research. Boca Ratón: CRC Press, p. 283–284.

Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, Kritas SK (2020) Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents 34(2): 327–331. https://doi.org/10.23812/CONTI-E

Dasgupta A, Kalhan A, Kalra S (2020) Long term complications and rehabilitation of COVID-19 patients. J Pak Med Assoc 70(Suppl 3)(5): S131-S135. https://doi.org/10.5455/JPMA.32

Deavall DG, Martin EA, Horner JM, Roberts R (2012) Drug-induced oxidative stress and toxicity. J Toxicol 2012: 645460. https://doi.org/10.1155/2012/645460

Delgado-Roche L, Mesta F (2020) Oxidative stress as key player in severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Arch Med Res 51(5): 384–387. https://doi.org/10.1016/j.arcmed.2020.04.019

Di Meo S, Reed TT, Venditti P, Victor VM (2016) Role of ROS and RNS sources in physiological and pathological conditions. Oxid Med Cell Longev 2016: 1245049. https://doi.org/10.1155/2016/1245049

Dosch SF, Mahajan SD, Collins AR (2009) SARS coronavirus spike protein-induced innate immune response occurs via activation of the NF-kappaB pathway in human monocyte macrophages in vitro. Virus Res 142(1-2): 19–27. https://doi.org/10.1016/j.virusres.2009.01.005

Dysangco A, Liu Z, Stein JH, Dubé MP, Gupta SK (2017) HIV infection, antiretroviral therapy, and measures of endothelial function, inflammation, metabolism, and oxidative stress. PLoS One 12(8): e0183511. https://doi.org/10.1371/journal.pone.0183511

Erdelmeier I, Gérard-Monnier D, Yadan JC, Chaudière J (1998) Reactions of N-methyl-2-phenylindole with malondialdehyde and 4-hydroxyalkenals. Mechanistic aspects of the colorimetric assay of lipid peroxidation. Chem Res Toxicol 11(10): 1184–1194. https://doi.org/10.1021/tx970180z

Fakhri S, Nouri Z, Moradi SZ, Farzaei MH (2020) Astaxanthin, COVID-19 and immune response: Focus on oxidative stress, apoptosis and autophagy. Phytother Res 34(11): 2790–2792. https://doi.org/10.1002/ptr.6797

Fang FC (2011) Antimicrobial actions of reactive oxygen species. mBio 2(5): e00141–11. https://doi.org/10.1128/mBio.00141-11

Gadotti AC, Lipinski AL, Vasconcellos FT, Marqueze LF, Cunha EB, Campos AC, Oliveira CF, Amaral AN, Baena CP, Telles JP, Tuon FF, Pinho RA (2021) Susceptibility of the patients infected with Sars-Cov2 to oxidative stress and possible interplay with severity of the disease. Free Radic Biol Med 165: 184–190. https://doi.org/10.1016/j.freeradbiomed.2021.01.044

Gemelli Against COVID-19 Post-Acute Care Study Group (2020) Post-COVID-19 global health strategies: the need for an interdisciplinary approach. Aging Clin Exp Res 32(8): 1613–1620. https://doi.org/10.1007/s40520-020-01616-x

Goud PT, Bai D, Abu-Soud HM (2021) A multiple-hit hypothesis involving reactive oxygen species and myeloperoxidase explains clinical deterioration and fatality in COVID-19. Int J Biol Sci 17(1): 62–72. https://doi.org/10.7150/ijbs.51811

Granger DL, Taintor RR, Boockvar KS, Hibbs JB, Jr. (1996) Measurement of nitrate and nitrite in biological samples using nitrate reductase and Griess reaction. Methods Enzymol 268: 142-151. https://doi.org/10.1016/s0076-6879(96)68016-1

Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L (2020) Management of post-acute covid-19 in primary care. BMJ 370: m3026. https://doi.org/10.1136/bmj.m3026

Ifrim DC, Quintin J, Joosten LA, Jacobs C, Jansen T, Jacobs L, Gow NA, Williams DL, van der Meer JW, Netea MG (2014) Trained immunity or tolerance: opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors. Clin Vaccine Immunol 21(4): 534–545. https://doi.org/10.1128/CVI.00688-13

Imai Y, Kuba K, Neely GG, Yaghubian-Malhami R, Perkmann T, van Loo G, Ermolaeva M, Veldhuizen R, Leung YH, Wang H, Liu H, Sun Y, Pasparakis M, Kopf M, Mech C, Bavari S, Peiris JS, Slutsky AS, Akira S, Hultqvist M, Holmdahl R, Nicholls J, Jiang C, Binder CJ, Penninger JM (2008) Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 133(2): 235–249. https://doi.org/10.1016/j.cell.2008.02.043

Kalem AK, Kayaaslan B, Neselioglu S, Eser F, Hasanoglu İ, Aypak A, Akinci E, Akca HN, Erel O, Guner R (2021) A useful and sensitive marker in the prediction of COVID-19 and disease severity: Thiol. Free Radic Biol Med 166: 11–17. https://doi.org/10.1016/j.freeradbiomed.2021.02.009

Kemp HI, Corner E, Colvin LA (2020) Chronic pain after COVID-19: implications for rehabilitation. Br J Anaesth 125(4): 436–440. https://doi.org/10.1016/j.bja.2020.05.021

Khomich OA, Kochetkov SN, Bartosch B, Ivanov AV (2018) Redox biology of respiratory viral infections. Viruses 10(8): 392. https://doi.org/10.3390/v10080392

Kobayashi EH, Suzuki T, Funayama R, Nagashima T, Hayashi M, Sekine H, Tanaka N, Moriguchi T, Motohashi H, Nakayama K, Yamamoto M (2016) Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat Commun 7: 11624. https://doi.org/10.1038/ncomms11624

Kosanovic T, Sagic D, Djukic V, Pljesa-Ercegovac M, Savic-Radojevic A, Bukumiric Z, Lalosevic M, Djordjevic M, Coric V, Simic T (2021) Time course of redox biomarkers in COVID-19 pneumonia: Relation with inflammatory, multiorgan impairment biomarkers and CT findings. Antioxidants (Basel) 10(7): 1126. https://doi.org/10.3390/antiox10071126

Lee C (2018) Therapeutic modulation of virus-induced oxidative stress via the Nrf2-dependent antioxidative pathway. Oxid Med Cell Longev 2018: 6208067. https://doi.org/10.1155/2018/6208067

Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, Gargiulo G, Testa G, Cacciatore F, Bonaduce D, Abete P (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13: 757–772. https://doi.org/10.2147/CIA.S158513

Liu C, Zhou Q, Li Y, Garner LV, Watkins SP, Carter LJ, Smoot J, Gregg AC, Daniels AD, Jervey S, Albaiu D (2020) Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Cent Sci 6(3): 315–331. https://doi.org/10.1021/acscentsci.0c00272

Majewska E, Kasielski M, Luczynski R, Bartosz G, Bialasiewicz P, Nowak D (2004) Elevated exhalation of hydrogen peroxide and thiobarbituric acid reactive substances in patients with community acquired pneumonia. Respir Med 98(7): 669–676. https://doi.org/10.1016/j.rmed.2003.08.015

Mao C, Yuan JQ, Lv YB, Gao X, Yin ZX, Kraus VB, Luo JS, Chei CL, Matchar DB, Zeng Y, Shi XM (2019) Associations between superoxide dismutase, malondialdehyde and all-cause mortality in older adults: a community-based cohort study. BMC Geriatr 19(1): 104. https://doi.org/10.1186/s12877-019-1109-z

Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47(3): 469–474. https://doi.org/10.1111/j.1432-1033.1974.tb03714.x

Marrocco I, Altieri F, Peluso I (2017) Measurement and clinical significance of biomarkers of oxidative stress in humans. Oxid Med Cell Longev 2017: 6501046. https://doi.org/10.1155/2017/6501046

Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB (2014) Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 20(7): 1126–1167. https://doi.org/10.1089/ars.2012.5149

Muhammad Y, Kani YA, Iliya S, Muhammad JB, Binji A, El-Fulaty Ahmad A, Kabir MB, Umar Bindawa K, Ahmed A (2021) Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria. SAGE Open Med 9: 2050312121991246. https://doi.org/10.1177/2050312121991246

Muralidharan S, Mandrekar P (2013) Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation. J Leukoc Biol 94(6): 1167–1184. https://doi.org/10.1189/jlb.0313153

Palipoch S, Koomhin P (2015) Oxidative stress-associated pathology: A review. Sains Malays 44(10): 1441–1451.

Patlevič P, Vašková J, Švorc P, Jr., Vaško L, Švorc P (2016) Reactive oxygen species and antioxidant defense in human gastrointestinal diseases. Integr Med Res 5(4): 250–258. https://doi.org/10.1016/j.imr.2016.07.004

Phaniendra A, Jestadi DB, Periyasamy L (2015) Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem 30(1): 11–26. https://doi.org/10.1007/s12291-014-0446-0

Pickering AM, Vojtovich L, Tower J, A Davies KJ (2013) Oxidative stress adaptation with acute, chronic, and repeated stress. Free Radic Biol Med 55: 109–118. https://doi.org/10.1016/j.freeradbiomed.2012.11.001

Pincemail J, Cavalier E, Charlier C, Cheramy-Bien JP, Brevers E, Courtois A, Fadeur M, Meziane S, Goff CL, Misset B, Albert A, Defraigne JO, Rousseau AF (2021) Oxidative stress status in COVID-19 patients hospitalized in intensive care unit for severe pneumonia. A pilot study. Antioxidants (Basel) 10(2): 257. https://doi.org/10.3390/antiox10020257

Pisoschi AM, Pop A (2015) The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem 97: 55–74. https://doi.org/10.1016/j.ejmech.2015.04.040

Polonikov A (2020) Endogenous deficiency of glutathione as the most likely cause of serious manifestations and death in COVID-19 patients. ACS Infect Dis 6(7): 1558–1562. https://doi.org/10.1021/acsinfecdis.0c00288

Schaefer L (2014) Complexity of danger: the diverse nature of damage-associated molecular patterns. J Biol Chem 289(51): 35237–35245. https://doi.org/10.1074/jbc.R114.619304

Schieber M, Chandel NS (2014) ROS function in redox signaling and oxidative stress. Curr Biol 24(10): R453–R462. https://doi.org/10.1016/j.cub.2014.03.034

Sebastiano M, Chastel O, de Thoisy B, Eens M, Costantini D (2016) Oxidative stress favours herpes virus infection in vertebrates: a meta-analysis. Curr Zool 62(4): 325–332. https://doi.org/10.1093/cz/zow019

Sies H, Berndt C, Jones DP (2017) Oxidative stress. Annu Rev Biochem 86: 715–748. https://doi.org/10.1146/annurev-biochem-061516-045037

Sies H, Jones DP (2020) Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol 21(7): 363–383. https://doi.org/10.1038/s41580-020-0230-3

Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP (2020) The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol 20(6): 363–374. https://doi.org/10.1038/s41577-020-0311-8

Vlahos R, Stambas J, Bozinovski S, Broughton BR, Drummond GR, Selemidis S (2011) Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation. PLoS Pathog 7(2): e1001271. https://doi.org/10.1371/journal.ppat.1001271

WHO (2020) Coronavirus disease (COVID-2019) situation reports 2020 [cited 13/7/2022][Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports

Witko-Sarsat V, Friedlander M, Nguyen Khoa T, Capeillère-Blandin C, Nguyen AT, Canteloup S, Dayer JM, Jungers P, Drüeke T, Descamps-Latscha B (1998) Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure. J Immunol 161(5): 2524–2532.

Xuan Y, Gào X, Anusruti A, Holleczek B, Jansen E, Muhlack DC, Brenner H, Schöttker B (2019) Association of serum markers of oxidative stress with incident major cardiovascular events, cancer incidence, and all-cause mortality in type 2 diabetes patients: Pooled results from two cohort studies. Diabetes Care 42(8): 1436–1445. https://doi.org/10.2337/dc19-0292

Ye Q, Wang B, Mao J (2020) The pathogenesis and treatment of the `Cytokine Storm’ in COVID-19. J Infect 80(6): 607–613. https://doi.org/10.1016/j.jinf.2020.03.037

Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579(7798): 270–273. https://doi.org/10.1038/s41586-020-2012-7

© 2023 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Sonchus arvensis L. against SARS-CoV-2 infection

Pharmaceutical Science, , , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1126-1138, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1489_10.6.1126

Original Article

Molecular simulation of compounds from n-hexane fraction of Sonchus arvensis L. leaves as SARS-CoV-2 antiviral through inhibitor activity targeting strategic viral protein

[Simulación molecular de compuestos de la fracción de n-hexano de las hojas de Sonchus arvensis L. como antivirales del SARS-CoV-2 a través de la actividad inhibidora dirigida a la proteína viral estratégica]

Dwi Kusuma Wahyuni1,2*, Sumrit Wacharasindhu3, Wichanee Bankeeree2, Hunsa Punnapayak2, Hery Purnobasuki1, Junairiah1, Arif NM Ansori4, Viol Dhea Kharisma1,5, Arli Aditya Parikesit6, Listyani Suhargo1*, Sehanat Prasongsuk1,2*

1Department of Biology, Faculty of Science and Technology, Universitas Airlangga Surabaya, East Java, 60115, Indonesia.

2Plant Biomass Utilization Research Unit, Department of Botany, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.

3Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok,10330, Thailand.

4Professor Nidom Foundation, Surabaya, East Java, 60115, Indonesia.

5Computational Virology Research Unit, Division of Molecular Biology and Genetics, Generasi Biologi Indonesia Foundation, Gresik, East Java, 61171, Indonesia.

6Department of Bioinformatics, School of Life Science, Indonesia International Institute for Life Sciences, Jakarta, 13210, Indonesia.

*E-mail: dwi-k-w@fst.unair.ac.id (DKW), listyani-s@fst.unair.ac.id (LS), sehanat.p@chula.ac.th (SP)

Abstract

Context: COVID-19 was caused by the spread and transmission of SARS-CoV-2 at the end of 2019 until now. The problem comes when antiviral drugs have not yet been found and patients infected with SARS-CoV-2 can trigger a cytokine storm condition due to the effects of viral replication. Indonesia has various kinds of medicinal plants, such as Sonchus arvensis L., which are used as medicinal plants.

Aims: To analyze the activity of the inhibitor as SARS-CoV-2 antiviral agents from n-hexane fractions of S. arvensis leaves.

Methods: The sample was collected from GC-MS analysis, PubChem, and Protein Databank database, then drug-likeness identification using Lipinski Rule of Five server and bioactive prediction of bioactive compounds as inhibitor activity was conducted by Molinspiration server. Furthermore, the docking simulation was performed using PyRx 0.9.9 software to determine the binding activity, molecular interaction by Discovery Studio software to identify position and interaction type, 3D molecular visualization by PyMol 2.5. software, and dynamic by CABS-flex 2.0 server to predict interaction stability.

Results: α-Amyrin and β-amyrin from n-hexane fractions of S. arvensis leaves had activity as SARS-CoV-2 inhibitors through interactions on helicase, RdRp, Mpro, and RBD-Spike, both compounds had more negative binding affinity than control drug and can produce stable chemical bond interactions in the ligand-protein complexes. However, the results were merely computational, so they must be validated through an in vivo and in vitro research approach.

Conclusions: Sonchus arvensis L. leaves were predicted to have SARS-CoV-2 antiviral through inhibitor activity by α-amyrin and β-amyrin.

Keywords: antiviral; bioinformatics; SARS-CoV-2; Sonchus arvensis L.

jppres_pdf_free

Resumen

Contexto: La propagación y la transmisión del SARS-CoV-2 han sido causadas por el COVID-19 desde finales de 2019 hasta ahora. El problema surge cuando aún no se han encontrado medicamentos antivirales y los pacientes infectados por el SARS-CoV-2 pueden desencadenar una condición de tormenta de citocinas debido a los efectos de la replicación viral. Indonesia tiene varios tipos de plantas medicinales, como Sonchus arvensis L., que se utilizan como plantas medicinales.

Objetivos: Analizar la actividad inhibidora de SARS-CoV-2 de fracciones de n-hexano de las hojas de S. arvensis.

Métodos: La muestra se recogió del análisis GC-MS, PubChem y la base de datos Protein Databank, luego se identificó la similitud de los fármacos utilizando el servidor Lipinski Rule of Five y se realizó la predicción de los compuestos bioactivos como actividad inhibidora mediante el servidor Molinspiration. Además, se realizó la simulación de acoplamiento mediante el software PyRx 0.9.9 para determinar la actividad de unión, la interacción molecular mediante el software Discovery Studio para identificar la posición y el tipo de interacción, la visualización molecular 3D mediante el software PyMol 2.5. y la dinámica mediante el servidor CABS-flex 2.0 para predecir la estabilidad de la interacción.

Resultados: La α-amirina y la β-amirina de las fracciones de n-hexano de las hojas de S. arvensis tuvieron actividad como inhibidores del SARS-CoV-2 a través de las interacciones en la helicasa, RdRp, Mpro y RBD-Spike, ambos compuestos tuvieron más afinidad de unión negativa que el fármaco de control y pueden producir interacciones de enlace químico estables en los complejos ligando-proteína. Sin embargo, los resultados fueron meramente computacionales, por lo que deben ser validados mediante un enfoque de investigación in vivo e in vitro.

Conclusiones: Se predijo que las hojas de S. arvensis tienen actividad antiviral contra el SARS-CoV-2 a través de la actividad inhibidora de la α-amirina y la β-amirina.

Palabras Clave: antiviral; bioinformática; SARS-CoV-2; Sonchus arvensis L.

jppres_pdf_free

Download the PDF file .

 
Citation Format: Wahyuni DK, Wacharasindhu S, Bankeeree W, Punnapayak H, Parikesit AA, Kharisma VD, Ansori ANM, Suhargo L, Prasongsuk S (2022) Molecular simulation of compounds from n-hexane fraction of Sonchus arvensis L. leaves as SARS-CoV-2 antiviral through inhibitor activity targeting strategic viral protein. J Pharm Pharmacogn Res 10(6): 1126–1138. https://doi.org/10.56499/jppres22.1489_10.6.1126
References

Ahamed T, Rahman SKM, Shohae AM (2017) Thin layer chromatographic profiling and phytochemical screening of six medicinal plants in Bangladesh. Int J Biosci 11(1): 131-140. https://doi.org/10.12692/ijb/11.1.131-140

Ahmad B, Batool M, Ain QU, Kim MS, Choi S (2021) Exploring the binding mechanism of PF-07321332 SARS-CoV-2 protease inhibitor through molecular dynamics and binding free energy simulations. Int J Mol Sci 22(17): 9124. https://doi.org/10.3390/ijms22179124

Aldakheel RK, Rehman S, Almessiere MA, Khan FA, Gondal MA, Mostafa A, Baykal A (2020) Bactericidal and in vitro cytotoxicity of Moringa oleifera seed extract and its elemental analysis using laser-induced breakdown spectroscopy. Pharmaceuticals 13(8): 193. https://doi.org/10.1101/2020.04.15.042663

Ali KS, Mohammed ASA, Munayem RT (2017) Phytochemical screening and thin layer chromatography of Acacia etbaica ssp. uncinata leaves. World J Pharm Res 6(12): 1278-1283. https://doi.org/10.20959/wjpr201712-9772

Ansori ANM, Fadholly A, Proboningrat A, Hayaza S, Susilo RJK, Naw SW, Posa GAV, Yusrizal YF, Sibero MT, Sucipto TH, Soegijanto S (2021a) In vitro antiviral activity of Pinus merkusii (Pinaceae) stem bark and cone against dengue virus type-2 (DENV-2). Res J Pharm Technol 14(7): 3705-3708. http://dx.doi.org/10.52711/0974-360X.2021.00641

Ansori ANM, Kharisma VD, Fadholly A, Tacharina MR, Antonius Y, Parikesit AA (2021b) Severe acute respiratory syndrome coronavirus-2 emergence and its treatment with alternative medicines: A review. Res J Pharm Technol 14(10): 5551-5557. https://doi.org/10.52711/0974-360X.2021.00967

Ansori ANM, Susilo RJK, Hayaza S (2021c) Biological activity investigation of phytocomponents in mangosteen (Garcinia mangostana L.): in silico study. Indian J Forensic Med Toxicol 15(1): 847-851. https://doi.org/10.37506/ijfmt.v15i1.13522

Benet LZ, Hosey CM, Ursu O, Oprea TI (2016) BDDCS, the rule of 5 and drugability. Adv Drug Deliv Rev 101:89-98. https://doi.org/10.1016/j.addr.2016.05.007

Biskup E, Golebiowski R, Stepnowski P, Lojkowska E (2012) Triterpenoid α-amyrin stimulates proliferation of human keratinocytes but does not protect them against UVB damage. Acta Biochim Pol 59(2): 255–260.

Borg J, Toazara J, Hietter H, Henry M, Schmitt G, Luu B (1987) Neurotrophic effect of naturally occurring long-chain fatty alcohols on cultured CNS. Neurons 213(2): 406-410. https://doi.org/10.1016/0014-5793(87)81531-4

Bourgonje AR, Abdulle AE, Timens W, Hillebrands JL, Navis GJ, Gordijn SJ, Bolling MC, Dijkstra G, Voors AA, Osterhaus AD, van der Voort PH, Mulder DJ, van Goor H (2020) Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). J Pathol 251(3): 228-248. https://doi.org/10.1002/path.5471

Delyan E (2016) Analysis of composition of volatile compounds of field sow thistle (Sonchus arvensis L.) leaves using the method of gas chromatography with mass-detection. J Pharm Innov 5: 118-121.

Dhama K, Khan S, Tiwari R, Sircar S, Bhat S, Malik YS, Singh KP, Chaicumpa W, Bonilla-Aldana DK, Rodriguez-Morales AJ (2020) Coronavirus disease 2019-COVID-19. Clin Microbiol Rev 33(4): e00028-20. https://doi.org/10.1128/CMR.00028-20

Dibha AF, Wahyuningsih S, Ansori ANM, Kharisma VD, Widyananda MH, Parikesit AA, Sibero MT, Probojati RT, Murtadlo AAA, Trinugroho JP, Sucipto TH, Turista DDR, Rosadi I, Ullah ME, Jakhmola V, Zainul R (2022) Utilization of secondary metabolites in algae Kappaphycus alvarezii as a breast cancer drug with a computational method. Pharmacog J 14(3): 536-543. https://doi.org/10.5530/pj.2022.14.68

Du X, Li Y, Xia YL, Ai SM, Liang J, Sang P, Ji XL, Liu SQ (2016). Insights into protein-ligand interactions: mechanisms, models, and methods. Int J Mol Sci 17(2): 144. https://doi.org/10.3390/ijms17020144

Duke JA (1992) Handbook of phytochemical constituents of GRAS herbs and other economic plants, CRC Press, Boca Raton, FL, USA.

Ekalu A, Ayo RGO, Habila JD, Hamisu (2019) Bioactivities of phaeophytin a, α-amyrin, and lupeol from Brachystelma togoense Schltr. J Turk Chem Soc 6(3): 411-418. https://doi.org/10.18596/jotcsa.571770

Elnakady YA, Rushdi AI, Franke R, Abutaha N, Ebaid H, Baabbad M, Omar MOM, Al Ghamdi AA (2017) Characteristics, chemical compositions and biological activities of propolis from Al-Bahah, Saudi Arabia. Sci Rep 7: 41453. https://doi.org/10.1038/srep41453

Gade S, Rajamanikyam M, Vadlapudi V, Nukala MK, Aluvala R, Giddigari C, Karanam NJ, Barua NC, Pandey R, Upadhayayula VSV, Srpadi P, Amanchy R, Upadhyayula SM (2017) Acetylcholinesterase inhibitory activity of stigmasterol & hexacosanol is responsible for larvicidal and repellent properties of Chromolaena odorata. Biochim Biophys Acta 1861(3): 541-550. https://doi.org/10.1016/j.bbagen.2016.11.044

Hassan NM, Alhossary AA, Mu Y, Kwoh CK (2017) Protein-ligand blind docking using QuickVina-W with inter-process spatio-temporal integration. Scie Rep 7(1): 15451. https://doi.org/10.1038/s41598-017-15571-7

Hendriani R, Sukandar EY, Anggadiredja K. Sukrasno (2015) In vitro evaluation of xanthine oxidase inhibitory activity of selected medicinal plants. Int J Pharm Clin 8: 235-238.

Imelda I, Azaria C, Lucretia T (2017) Protective effect of ethanol extract tempuyung leaf (Sonchus arvensis L.) against gentamicin induced renal injury viewed from blood ureum level. Med Health 1: 575-82. https://doi.org/10.28932/jmh.v1i6.555

Kabinger F, Stiller C, Schmitzová J, Dienemann C, Kokic G, Hillen HS, Höbartner C, Cramer P (2021) Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis. Nat Struct Mol Biol 28(9): 740-746. https://doi.org/10.1038/s41594-021-00651-0

Khan RA (2012) Evaluation of flavonoids and diverse antioxidant activities of Sonchus arvensis. Chem Cent J6(1): 126. https://doi.org/10.1186/1752-153X-6-126

Kharisma VD, Agatha A, Ansori ANM, Widyananda MH, Rizky WC, Dings TGA, Derkho M, Lykasova I, Antonius Y, Rosadi I, Zainul R (2022) Herbal combination from Moringa oleifera Lam. and Curcuma longa L. as SARS-CoV-2 antiviral via dual inhibitor pathway: A viroinformatics approach. J Pharm Pharmacogn Res 10(1): 138–146. https://doi.org/10.56499/jppres21.1174_10.1.138

Kharisma VD, Ansori ANM, Nugraha AP (2020) Computational study of ginger (Zingiber officinale) as E6 inhibitor in human papillomavirus type 16 (HPV-16) infection. Biochem Cell Arch 20 (Suppl 1): 3155-3159. https://doi.org/10.35124/bca.2020.20.S1.3155

Listiyani P, Kharisma VD, Ansori AN, Widyananda MH, Probojati RT, Murtadlo AA (2022) In silico phytochemical compounds screening of Allium sativum targeting the Mpro of SARS-CoV-2. Pharmacog J 14(3): 604-609. https://10.5530/pj.2022.14.78

Maio N, Lafont BAP, Sil D, Li Y, Bollinger JM Jr, Krebs C, Pierson TC, Linehan WM, Rouault TA (2021) Fe-S cofactors in the SARS-CoV-2 RNA-dependent RNA polymerase are potential antiviral targets. Science 373(6551): 236-241. https://doi.org/10.1126/science.abi5224

Murgolo N, Therien AG, Howell B, Klein D, Koeplinger K, Lieberman LA, Adam GC, Flynn J, McKenna P, Swaminathan G, Hazuda DJ, Olsen DB (2021) SARS-CoV-2 tropism, entry, replication, and propagation: considerations for drug discovery and development. PLoS Pathog 17(2): e1009225. https://doi.org/10.1371/journal.ppat.1009225

Niewolik D, Bednarczyk-Cwynar B, Ruszkowsk P, Sosnowski TR, Jaszcz K (2021) Bioactive betulin and PEG based polyanhydrides for use in drug delivery systems. Int J Mol Sci 22(3): 1090. https://doi.org/10.3390/ijms22031090

Ogwuche CE, Amupitan JO, Ayo RG (2014) Isolation and biological activity of the triterpene ß-amyrin from the aerial plant parts of Maesobotrya barteri (Baill). Med Chem 4: 729–733. https://doi.org/10.4172/2161-0444.1000221

Okoye NN, Ajaghaku DL, Okeke HN, Ilodigwe EE, Nworu CS, Okoye FBC (2014) Beta-amyrin and alpha-amyrin acetate isolated from the stem bark of Alstonia boonei display profound anti-inflammatory activity. Pharm Biol 52: 1478–1486. https://doi.org/10.3109/13880209.2014.898078

Prahasanti C, Nugraha AP, Kharisma VD, Ansori ANM, Devijanti R, Ridwan TPSP, Ramadhani NF, Narmada IB, Ardani IGAW, Noor TNEBA (2021) A bioinformatic approach of hydroxyapatite and polymethylmethacrylate composite exploration as dental implant biomaterial. J Pharm Pharmacog Res 9(5): 746-754. https://doi.org/10.56499/jppres21.1078_9.5.746

Proboningrat A, Kharisma VD, Ansori ANM, Rahmawati R, Fadholly A, Posa GAV, Sudjarwo SA, Rantam FA, Achmad AB (2022) In silico study of natural inhibitors for human papillomavirus-18 E6 protein. Res J Pharm Technol 15(3): 1251-1256. https://doi.org/10.52711/0974-360X.2022.00209

Putra WE, Kharisma VD, Susanto H (2020) Potential of Zingiber officinale bioactive compounds as inhibitory agent against the IKK-B. AIP Conf Proc 2231(1): 040048. https://doi.org/10.1063/5.0002478

Ramos RS, Borges RS, de Souza JSN, Araujo IF, Chaves MH, Santos CBR (2022) Identification of potential antiviral inhibitors from hydroxychloroquine and 1,2,4,5-tetraoxanes analogues and investigation of the mechanism of action in SARS-CoV-2. Int J Mol Sci 23(3): 1781. https://doi.org/10.3390/ijms23031781

Rumondang M, Kusrini D, Fachriyah E (2013) Isolation, identification and antibacterial test of triterpenoid compounds from n-hexane extract of tempuyung leaves (Sonchus arvensis L.). Pharm Sci 05: 506-507.

Saito M, Kinoshita Y, Satoh I, Bex A, Bertaccini A (2006) Ability of cyclohexenonic long-chain fatty alcohol to reverse diabetes-induced cystopathy in the rat. Eur Urol 51(2): 479-488. https://doi.org/10.1016/j.eururo.2006.06.024

Shaheen U, Akka J, Hinore JS, Girdhar A, Bandaru S, Sumithnath TG, Nayarisseri A, Munshi A (2015) Computer aided identification of sodium channel blockers in the clinical treatment of epilepsy using molecular docking tools. Bioinformation 11(3): 131-137. https://doi.org/10.6026/97320630011131

Shamsi A, Mohammad T, Anwar S, Amani S, Khan MS, Husain FM, Rehman MT, Islam A, Hassan MI (2021) Potential drug targets of SARS-CoV-2: From genomics to therapeutics. Int J Biol Macromol 177: 1-9. https://doi.org/10.1016/j.ijbiomac.2021.02.071

Sharma K, Zafar R (2015) Occurrence of taraxerol and taraxasterol in medicinal plants. Pharmacog Rev 9(17): 19-23. https://doi.org/10.4103/0973-7847.156317

Shivanika C, Deepak KS, Venkataraghavan R, Pawan T, Sumitha A, Brindha DP (2022) Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease. J Biomol Struct Dyn 40(2): 585-611. https://doi.org/10.1080/07391102.2020.1815584

Singh AK, Singh A, Singh R, Misra A (2021) Molnupiravir in COVID-19: A systematic review of literature. Diabetes Metab Syndr 15(6): 102329. https://doi.org/10.1016/j.dsx.2021.102329

Sunil C, Irudayaraj SS, Duraipandiyan V, AlDhabi NA, Agastian P, Ignacimuthu S (2014) Antioxidant and free radical scavenging effects of ß-amyrin isolated from S. cochinchinensis Moore. leaves. Ind Crops Prod 61: 510–516. https://doi.org/10.1016/j.indcrop.2014.07.005

Tolstikov GA, Flekhter OB, Shultz EE, Baltina LA, Tolstikov AG (2005) Betulin and its derivatives. Chemistry and biological activity. Chem Sustainable Dev 13: 1-29.

Wahyuni DK, Lestari S, Kuncoro EP, Purnobasuki H (2020b) Callus induction and its metabolite profiles of Sonchus arvensis L. under temperature treatment. Ann Biol 36(2): 299–303.

Wahyuni DK, Purnobasuki H, Kuncoro EP, Ekasari W (2020a) Callus induction of Sonchus arvensis L. and its antiplasmodial activity. Afr J Infect 14: 1-7. https://doi.org/10.21010/ajid.v14i1.1

Wahyuni DK, Rahayu S, Purnama PR, Saputro TB, Suharyanto, Wijayanti N (2019) Morpho-anatomical structure and DNA barcode of Sonchus arvensis L. Biodiversitas 20(24): 17-26. https://doi.org/10.13057/biodiv/d200841

Wahyuni DK, Rahayu S, Zaidan AH, Ekasari W, Prasongsuk S, Purnobasuki H (2021) Growth, secondary metabolite production, and in vitro antiplasmodial activity of Sonchus arvensis L. callus under dolomite [CaMg(CO3)2] treatment. PLoS One 16: e0254804. https://doi.org/10.1371/journal.pone.0254804

Widyananda MH, Pratama SK, Samoedra RS, Sari FN, Kharisma VD, Ansori ANM, Antonius Y (2021) Molecular docking study of sea urchin (Arbacia lixula) peptides as multi-target inhibitor for non-small cell lung cancer (NSCLC) associated proteins. J Pharm Pharmacog Res 9(4): 484-496. https://doi.org/10.56499/jppres21.1047_9.4.484

Wijaya RM, Hafidzhah MA, Kharisma VD, Ansori ANM, Parikesit AA (2021) COVID-19 in silico drug with Zingiber officinale natural product compound library targeting the Mpro protein. Makara J Sci 25(3): 162-171. https://doi.org/10.7454/mss.v25i3.1244

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Phyllanthus tenellus and Kaempferia parviflora compounds inhibit SARS-CoV-2

Pharmaceutical Science, , , , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1103-1116, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1485_10.6.1103

Original Article

Phyllanthus tenellus Roxb. and Kaempferia parviflora Wall. ex Baker compounds as inhibitors of SARS-CoV-2 main protease and RNA-dependent RNA polymerase: A molecular docking study

[Compuestos de Phyllanthus tenellus Roxb. y Kaempferia parviflora Wall. ex Baker como inhibidores de la proteasa principal del SARS-CoV-2 y de la ARN polimerasa dependiente de ARN: Un estudio de acoplamiento molecular]

Suhaina Supian*, Muhamad Aizuddin Ahmad, Lina Rozano, Machap Chandradevan, Zuraida Ab Rahman

Biotechnology and Nanotechnology Research Centre, Malaysian Agricultural Research and Development Institute (MARDI), Serdang 43400, Selangor, Malaysia.

*E-mail: suhaina@mardi.gov.my

Abstract

Context: The outbreak of a novel coronavirus, SARS-CoV-2 has caused an unprecedented COVID-19 pandemic. To put an end to this pandemic, effective antivirals should be identified or developed for COVID-19 treatment. However, specific and effective antivirals or inhibitors against SARS-CoV-2 are still lacking.

Aims: To evaluate bioactive compounds from Phyllanthus tenellus and Kaempferia parviflora as inhibitorsagainst two essential SARS-CoV-2 proteins, main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), through molecular docking studies and to predict the drug-likeness properties of the compounds.

Methods: The inhibition potential and interaction of P. tenellus and K. parviflora compounds against Mpro and RdRp were assessed through molecular docking. The drug-likeness properties of the compounds were predicted using SwissADME and AdmetSAR tools.

Results: Rutin and ellagic acid glucoside from P. tenellus and 4-hydroxy-6-methoxyflavone and 5-hydroxy-3,7,4’-trimethoxyflavone from K. parviflora exhibited the highest binding conformations to Mpro by interacting with its substrate binding site that was predicted to halt the Mpro activity. As for RdRp, ellagitannin and rutin from P. tenellus and peonidin and 5,3’-dihydroxy-3,7,4’-trimethoxyflavone from K. parviflora were the best-docked compounds that bound to the RdRp catalytic domain (Asp760 and Asp761) and NTP-entry channel that were anticipated to stop RNA polymerization. However, in the context of drug developability, 4-hydroxy-6-methoxyflavone, 5-hydroxy-3,7,4’-trimethoxyflavone, peonidin and 5,3’-dihydroxy-3,7,4’-trimethoxyflavone from K. parviflora were highly potential to be oral active drugs compared to rutin, ellagic acid glucoside and ellagitannin from P. tenellus.

Conclusions: P. tenellus and K. parviflora compounds, particularly the aforementioned compounds, were suggested as potential inhibitors of SARS-CoV-2 Mpro and RdRp.

Keywords: antiviral; compounds; COVID-19; in silico; Kaempferia parviflora; Phyllanthus tenellus.

jppres_pdf_free

Resumen

Contexto: El brote de un nuevo coronavirus, el SARS-CoV-2, ha provocado una pandemia de COVID-19 sin precedentes. Para poner fin a esta pandemia, es necesario identificar o desarrollar antivirales eficaces para el tratamiento del COVID-19. Sin embargo, aún se carece de antivirales o inhibidores específicos y eficaces contra el SARS-CoV-2.

Objetivos: Evaluar compuestos bioactivos de Phyllanthus tenellus y Kaempferia parviflora como inhibidores contra dos proteínas esenciales del SARS-CoV-2, la proteasa principal (Mpro) y la ARN polimerasa dependiente del ARN (RdRp), mediante estudios de acoplamiento molecular y predecir las propiedades de similitud con los fármacos de los compuestos.

Métodos: El potencial de inhibición y la interacción de los compuestos de P. tenellus y K. parviflora contra la Mpro y la RdRp fueron evaluados mediante docking molecular. Las propiedades de semejanza de los compuestos se predijeron mediante las herramientas SwissADME y AdmetSAR.

Resultados: La rutina y el glucósido del ácido elágico de P. tenellus y la 4-hidroxi-6-metoxiflavona y la 5-hidroxi-3,7,4′-trimetoxiflavona de K. parviflora mostraron las conformaciones de unión más altas a Mpro al interactuar con su sitio de unión al sustrato que se predijo para detener la actividad de Mpro. En cuanto a la RdRp, la elagitanina y la rutina de P. tenellus y la peonidina y la 5,3′-dihidroxi-3,7,4′-trimetoxiflavona de K. parviflora fueron los compuestos mejor acoplados que se unieron al dominio catalítico de la RdRp (Asp760 y Asp761) y al canal de entrada NTP que se anticipó que detendría la polimerización del ARN. Sin embargo, en el contexto del desarrollo de fármacos, la 4-hidroxi-6-metoxiflavona, la 5-hidroxi-3,7,4′-trimetoxiflavona, la peonidina y la 5,3′-dihidroxi-3,7,4′-trimetoxiflavona de K. parviflora tendrían un gran potencial para ser fármacos activos por vía oral en comparación con la rutina, el glucósido de ácido elágico y la elagitanina de P. tenellus.

Conclusiones: Los compuestos de P. tenellus y K. parviflora, en particular los mencionados, fueron sugeridos como potenciales inhibidores de Mpro y RdRp del SARS-CoV-2.

Palabras Clave: antiviral; compuestos; COVID-19; in silico; Kaempferia parviflora; Phyllanthus tenellus.

jppres_pdf_free

Download the PDF file .

 
Citation Format: Supian S, Ahmad MA, Rozano L, Chandradevan M, Ab Rahman Z (2022) Phyllanthus tenellus Roxb. and Kaempferia parviflora Wall. ex Baker compounds as inhibitors of SARS-CoV-2 main protease and RNA-dependent RNA polymerase: A molecular docking study. J Pharm Pharmacogn Res 10(6): 1103–1116. https://doi.org/10.56499/jppres22.1485_10.6.1103
References

Aftab SO, Ghouri MZ, Masood MU, Haider Z, Khan Z, Ahmad A, Munawar N (2020)Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach. J Transl Med 18(1): 275. https://doi.org/10.1186/s12967-020-02439-0

Amin ML (2013) P-glycoprotein inhibition for optimal drug delivery. Drug Target Insights 7: 27–34. https://doi.org/10.33393/dti.2013.1349

Babar M, Najam‑Us‑Sahar SZ, Ashraf M, Kazi AG (2013) Antiviral drug therapy – Exploiting medicinal plants. J Antivir Antiretrovir 5: 28–36. https://doi.org/10.4172/2155-6113.1000215

Ben-Shabat S, Yarmolinsky L, Porat D, Dahan A (2020) Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies. Drug Deliv Transl Res 10(2): 354–367. https://doi.org/10.1007/s13346-019-00691-6

Chen D, Li H, Li W, Feng S, Deng D (2018) Kaempferia parviflora and its methoxyflavones: Chemistry and biological activities. Evid Based Complement Alternat Med 2018: 4057456. https://doi.org/10.1155/2018/4057456

Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, Lee PW, Tang Y (2012) admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model 52(11): 3099–3105. https://doi.org/10.1021/ci300367a

Cheng PW, Ng LT, Chiang LC, Lin CC (2006) Antiviral effects of saikosaponins on human coronavirus 229E in vitro. Clin Exp Pharmacol Physiol 33(7): 612–616. https://doi.org/10.1111/j.1440-1681.2006.04415.x

Daina A, Zoete V (2016) A BOILED-Egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem 11: 1117–1121. https://doi.org/10.1002/cmdc.201600182

Eweas AF, Alhossary AA, Abdel-Moneim AS (2021) Molecular docking reveals ivermectin and remdesivir as potential repurposed drugs against SARS-CoV-2. Front Microbiol 11: 592908. https://doi.org/10.3389/fmicb.2020.592908

Farouk F, Shamma R (2019) Chemical structure modifications and nano-technology applications for improving ADME-Tox properties, a review. Arch Pharm Chem Life Sci 352(2): e1800213. https://doi.org/10.1002/ardp.201800213

Jin Z, Wang H, Duan Y, Yang H (2020) The main protease and RNA-dependent RNA polymerase are two prime targets for SARS-CoV-2. Biochem Biophys Res Commun 538: 63–71. https://doi.org/10.1016/j.bbrc.2020.10.091

Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, Wang T, Sun Q, Ming Z, Zhang L, Ge J, Zheng L, Zhang Y, Wang H, Zhu Y, Zhu C, Hu T, Hua T, Zhang B, Yang X, Li J, Yang H, Liu Z, Xu W, Guddat LW, Wang Q, Lou Z, Rao Z (2020) Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science 368: 779–782. https://doi.org/10.1126/science.abb7498

Gentile D, Patamia V, Scala A, Sciortino MT, Piperno A, Rescifina (2020) Putative inhibitors of SARS-CoV-2 main protease from a library of marine natural products: A virtual screening and molecular modeling study. Mar Drugs 18(4): 225. https://doi.org/10.3390/md18040225

Ghanimi R, Ouhammou A, El Atki Y, Cherkaoui M (2022) Molecular docking study of the main phytochemicals of some medicinal plants used against COVID-19 by the rural population of Al-Haouz region, Morocco. J Pharm Pharmacogn Res 10(2): 227–238. https://doi.org/10.56499/jppres21.1200_10.2.227

Goyal B, Goyal D (2020) Targeting the dimerization of the main protease of coronaviruses: A potential broad-spectrum therapeutic strategy. ACS Comb Sci 22(6): 297–305. https://doi.org/10.1021/acscombsci.0c00058

Kharisma VD, Aghata A, Ansori ANM, Widyananda MH, Rizky WC, Dings TGA, Derkho M, Lykasova I, Antonius Y, Rosadi I, Zainul R (2022) Herbal combination from Moringa oleifera Lam. and Curcuma longa L. as SARS-CoV-2 antiviral via dual inhibitor pathway: A viroinformatics approach. J Pharm Pharmacogn Res 10(1): 138–146. https://doi.org/10.56499/jppres21.1174_10.1.138

Lamb YN (2022) Nirmatrelvir plus ritonavir: first approval. Drugs 82:585–591. https://doi.org/10.1007/s40265-022-01692-5  

Long C, Romero ME, La Rocco D, Yu J (2021) Dissecting nucleotide selectivity in viral RNA polymerases. Comput Struct Biotechnol J 19: 3339–3348. https://doi.org/10.1016/j.csbj.2021.06.005

Martin R, Li J, Parvangada A, Perry J, Cihlar T, Mo H, Porter D, Svarovskaia E (2021) Genetic conservation of SARS-CoV-2 RNA replication complex in globally circulating isolates and recently emerged variants from humans and minks suggests minimal pre-existing resistance to remdesivir. Antiviral Res 188: 105033. https://doi.org/10.1016/j.antiviral.2021.105033

Mehrbod P, Hudy D, Shyntum D, Markowski J, Łos MJ, Ghavami S (2021) Quercetin as a natural therapeutic candidate for the treatment of influenza virus. Biomol 11(1): 10. https://doi.org/10.3390/biom11010010

Mohammad Zadeh N, Mashinchi Asl NS, Forouharnejad K, Ghadimi K, Parsa S, Mohammadi S, Omidi A (2021) Mechanism and adverse effects of COVID-19 drugs: a basic review. Int J Physiol Pathophysiol Pharmacol 13(4): 102–109.

Mohd Jusoh NH, Subki A, Yeap SK, Yap KC, Jaganath IB (2019) Pressurized hot water extraction of hydrosable tannins from Phyllanthus tenellus Roxb. BMC Chem 13(1): 134. https://doi.org/10.1186/s13065-019-0653-0

Nutan MM, Goel T, Das T, Malik S, Suri S, Rawat AKS, Srivastava SK, Tuli R, Malhotra S, Gupta SK (2013) Ellagic acid & gallic acid from Lagerstroemia speciosa L. inhibit HIV-1 infection through inhibition of HIV-1 protease & reverse transcriptase activity. Indian J Med Res 137: 540–548.

Oh C, Price J, Brindley MA, Widrlechner MP, Qu L, McCoy JA, Murphy P, Hauck C, Maury W (2011) Inhibition of HIV-1 infection by aqueous extracts of Prunella vulgaris L. Virol J 8: 188. https://doi.org/10.1186/1743-422X-8-188

Ortega JT, Suárez AI, Serrano ML, Baptista J, Pujol FH, Rangel HR (2017) The role of the glycosyl moiety of myricetin derivatives in anti-HIV-1 activity in vitro. AIDS Res Ther 14(1): 57. https://doi.org/10.1186/s12981-017-0183-6

Pitts J, Li J, Perry JK, Du Pont V, Riola N, Rodriguez L, Lu X, Kurhade C, Xie X, Camus G, Manhas S, Martin R, Shi PY, Cihlar T, Porter DP, Mo H, Maiorova E, Bilello JP (2022) Remdesivir and GS-441524 retain antiviral activity against delta, omicron, and other emergent SARS-CoV-2 variants. Antimicrob Agents Chemother 66(6): e0022222. https://doi.org/10.1128/aac.00222-22

Ritchie TJ, Macdonald SJ (2009) The impact of aromatic ring count on compound developability–are too many aromatic rings a liability in drug design? Drug Discovery Today 14(21/22): 1011–1020. https://doi.org/10.1016/j.drudis.2009.07.014

Shivanika C, Deepak Kumar S, Venkataraghavan R, Pawan T, Sumitha A, Brindha Devi P (2020) Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease. J Biomol Struct Dyn 40(2): 585–611. https://doi.org/10.1080/07391102.2020.1815584

Silva T, Veras Filho J, Lúcia CDAE, Antonia DSI, Albuquerque U, Cavalcante de Araújo E (2012) Acute toxicity study of stone-breaker (Phyllanthus tenellus Roxb.). Rev Cienc Farm 33: 205–210.

Sookkongwaree K, Geitmann M, Roengsumran S, Petsom A, Danielson UH (2006) Inhibition of viral proteases by Zingiberaceae extracts and flavones isolated from Kaempferia parviflora. Pharmazie 61(8): 717–721.

Sornpet B, Potha T, Tragoolpua Y, Pringproa K (2017) Antiviral activity of five Asian medicinal pant crude extracts against highly pathogenic H5N1 avian influenza virus. Asian Pac J Trop Med 10(9): 871–876. https://doi.org/10.1016/j.apjtm.2017.08.010

Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S, Zhou Y, Du L (2020) Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: Implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol Immunol 17(6): 613–620. https://doi.org/10.1038/s41423-020-0400-4

Tan WC, Jaganath IB, Manikam R, Sekaran SD (2013) Evaluation of antiviral activities of four local Malaysian Phyllanthus species against herpes simplex viruses and possible antiviral target. Int J Med Sci 10(13): 1817–1829. https://doi.org/10.7150/ijms.6902

Tao J, Hu Q, Yang J, Li R, Li X, Lu C, Chen C, Wang L, Shattock R, Ben K (2007) In vitro anti-HIV and -HSV activity and safety of sodium rutin sulfate as a microbicide candidate. Antiviral Res75(3): 227–233. https://doi.org/10.1016/j.antiviral.2007.03.008

te Velthuis AJ, Arnold JJ, Cameron CE, van den Worm SH, Snijder EJ (2010) The RNA polymerase activity of SARS-coronavirus nsp12 is primer dependent. Nucleic Acids Res 38(1): 203–214. https://doi.org/10.1093/nar/gkp904

te Velthuis AJ, van den Worm SH, Snijder EJ (2012) The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension. Nucleic Acids Res 40(4): 1737–1747. https://doi.org/10.1093/nar/gkr893

Vangeel L, Chiu W, De Jonghe S, Maes P, Slechten B, Raymenants J, André E, Leyssen P, Neyts J, Jochmans D (2022) Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern. Antiviral Res 198: 105252. https://doi.org/10.1016/j.antiviral.2022.105252

Xue B, Blocquel D, Habchi J, Uversky AV, Kurgan L, Uversky VN, Longhi S (2014) Structural disorder in viral proteins. Chem Rev 114(13): 6880–6911. https://doi.org/10.1021/cr4005692

Yenjai C, Prasanphen K, Daodee S, Wongpanich V, Kittakoop P (2004) Bioactive flavonoids from Kaempferia parviflora. Fitoterapia 75(1): 89–92. https://doi.org/10.1016/j.fitote.2003.08.017

Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, Becker S, Rox K, Hilgenfeld R (2020) Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved a-ketoamide inhibitors. Science 368: 409–412. https://doi.org/10.1126/science.abb3405

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL (2020) Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 588(7836): E6. https://doi.org/10.1038/s41586-020-2951-z

Zhu Z, Lian X, Su X, Wu W, Marraro GA, Zeng Y (2020) From SARS and MERS to COVID-19: A brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses. Respir Res 21(1): 224. https://doi.org/10.1186/s12931-020-01479-w

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Drug utilization in patients with SARS-CoV-2

Pharmaceutical Science, , , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 977-985, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1460_10.6.977

Original Article

Drug utilization in patients with SARS-CoV-2 in an intensive care unit

[Utilización de medicamentos en pacientes con SARS-CoV-2 en una unidad de cuidados intensivos]

Miguel Sevilla Méndez1, Ana M. Téllez López2, Giovanni Gómez Barragán3, Ivette Reyes Hernández2, Claudia Velázquez González2, Isis B. Bermúdez Camps2*

1Departamento de Servicios Farmacéuticos y la Unidad de Cuidados Intensivos Adulto, Hospital H+ Querétaro, Querétaro, Querétaro, México.

2Universidad Autónoma del Estado de Hidalgo, Instituto de Ciencias de la Salud, Departamento de Farmacia, Pachuca de Soto, Hidalgo, México.

3Hospital Infantil de México Federico Gómez, Ciudad de México, México.

*E-mail: isis_bermudes@uaeh.edu.mx

Abstract

Context: Prescription indication studies allow identifying the problems that arise during the use of the drug.

Aims: To evaluate the treatments used in patients diagnosed with SARS-CoV-2 infection hospitalized in critical care service, through a prescription indication study.

Methods: A longitudinal observational study of medication use of the indication-prescription type with elements of the therapeutic scheme and practical consequences was carried out. The sample was characterized from the sociodemographic, clinical, and pharmacotherapeutic points of view. The prescription was evaluated through the indicators: indication, therapeutic scheme, treatment individualization, and drug combinations. The detected adverse reactions were classified according to their causality by the Naranjo Algorithm, their severity, their clinical significance, and according to their mechanism by Rawlins and Thompson.

Results: In the sample (n = 77), the male gender predominated (79%) between 27-59 years old (64%), alcohol consumer (62%), hypertensive (33%) with long hospital stay (51%). A total of 417 medications were analyzed, being antibiotics (50.6%) the most prescribed. 73.4% of the therapeutic schemes were correct; however, 26.6% had problems with the therapeutic schemes due to incorrect doses, intervals, duration of treatment, and risky interactions. According to Rawlins and Thompson, two probable adverse reactions were detected, mild, non-serious, and type A and B.

Conclusions: The results obtained will allow the pharmaceutical professional to create risk matrices that guarantee a timely intervention in the health team to contribute to the rational and safe use of medicines in patients infected with SARS-CoV-2.

Keywords: COVID-19; drug utilization study; indication-prescription; intensive care unit; pharmacoepidemiology; pharmacological treatment.

jppres_pdf_free

Resumen

Contexto: Los estudios de indicación prescripción permiten identificar los problemas que se presentan durante el uso del medicamento.

Objetivos: Evaluar los tratamientos utilizados en pacientes con diagnóstico de infección por SARS-CoV-2 hospitalizados en el servicio de cuidados críticos, a través de un estudio de indicación de prescripción.

Métodos: Se realizó un estudio observacional longitudinal del uso de medicamentos, del tipo indicación-prescripción con elementos del esquema terapéutico y consecuencias prácticas. La muestra se caracterizó desde el punto de vista sociodemográfico, clínico y farmacoterapéutico. La prescripción se evaluó a través de los indicadores: indicación, esquema terapéutico, individualización del tratamiento y combinaciones de fármacos. Las reacciones adversas detectadas se clasificaron según su causalidad por el Algoritmo de Naranjo, su gravedad, su significado clínico y según su mecanismo por Rawlins y Thompson.

Resultados: En la muestra (n = 77), predominó el género masculino (79%) entre 27-59 años (64%), consumidor de alcohol (62%), hipertenso (33%) con larga estancia hospitalaria (51%). Se analizaron 417 medicamentos, siendo los antibióticos (50,6%) los más prescritos. El 73,4% de los esquemas terapéuticos fueron correctos, sin embargo, el 26,6% tuvo problemas con los esquemas terapéuticos debido al uso de dosis, intervalos y duración del tratamiento incorrectos, así como interacciones de riesgo. Se detectaron dos probables reacciones adversas, leves, no graves y tipo A y B según Rawlins y Thompson.

Conclusiones: Los resultados obtenidos permitirán al profesional farmacéutico crear matrices de riesgo que garanticen una intervención oportuna en el equipo de salud para contribuir al uso racional y seguro de medicamentos en pacientes infectados por SARS-CoV-2.

Palabras Clave: COVID-19; estudio de utilización de fármacos; farmacoepidemiología; indicación-prescripción; tratamiento farmacológico; unidad de cuidados intensivos.

jppres_pdf_free

Download the PDF file .

 

Citation Format: Sevilla MM, Téllez AL, Gómez GB, Reyes IH, Velázques CG, Bermudez IC (2022) Drug utilization in patients with SARS-CoV-2 in an intensive care unit. J Pharm Pharmacogn Res 10(6): 977–985. https://doi.org/10.56499/jppres22.1460_10.6.977
References

Abbas AK, Lichtman AH, Pober JS (2004) Enfermedades producidas por respuestas inmunitarias: hipersensibilidad y autoinmunidad. En: Inmunología Celular y Molecular, 5º Ed. España, Madrid: Sanunders-Elsevier, p. 411–431.

Amador JS, Hernández RA, Gutiérrez CM, Plaza JP (2018) Impact on the work of clinical pharmacist at the pharmacotherapy management of critically ill patient: Local experience in a clinical hospital. J Pharm Pharmacogn Res 6 (4): 285–298.

Amariles P, Madrigal J, Giraldo A (2021) Relevancia clínica de las interacciones medicamentosas: Propuesta de actualización de la clasificación en función de la gravedad y probabilidad de su ocurrencia. Rev Chilena Infectol 38(2): 304–305. http://dx.doi.org/10.4067/S0716-10182021000200304

Centers for Disease Control and Prevention (2021) Healthcare workers: Information on COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/index.html [Consulted 6 December 2021].

Chen N, Zhou M, Dong X, Qu J, Gong, F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L (2020) Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 5: 395. https://doi.org/10.1016/S0140-6736(20)30211-7

Cruz I, Sánchez M, Sánchez P, Jang I (2007) Trombocitopenia inducida por heparina. Rev Esp Cardiol 60: 1071–1082. https://doi.org/10.1157/13111239

Drugs.com (2021) Dexamethasone interactions. https://www.drugs.com/drug-interactions/dexamethasone.html [Consulted 6 December 2021].

Fantin R, Brenes G, Barboza C (2021) Defunciones por COVID-19: distribución por edad y universalidad de la cobertura médica en 22 países. Rev Panam Salud Publica 45: 42. https://doi.org/10.26633/RPSP.2021.42

Gace H (2012) Polifarmacia y morbilidad en adultos mayores. Rev Med Clin Condes 23: 31–35.

Gadi N, Samantha CW, Allison PS, Vaishali RM (2020) What’s sex got to do with COVID-19? Gender-based differences in the host immune response to coronaviruses. Front Immunol 11: 2147. https://doi.org/10.3389/fimmu.2020.02147

Garzón G, Montero L, García S, Jiménez C, Domínguez N, Mediavilla I (2020) Análisis descriptivo de los errores de medicación notificados en atención primaria: aprendiendo de nuestros errores. Aten Primaria 52: 233–239. https://doi.org/10.1016/j.aprim.2019.01.006

Gobierno de México (2022) COVID-19. México. Información general. https://datos.covid-19.conacyt.mx [Consulted 11 January 2022].

Gobierno de México (2021) Guía clínica para el tratamiento de la COVID-19 en México. https://coronavirus.gob.mx/wp-content/uploads/2021/08/GuiaTx_COVID19_ConsensoInterinstitucional_2021.08.03.pdf [Consulted 6 December 2021].

Hinks T, Cureton L, Knight R, Wang A, Cane J, Barber V, Black J, Dutton SJ, Melhorn J, Jabeen M, Moss P, Garlapati R, Baron T, Johnson G, Cantle F, Clarke D, Elkhodair S, Underwood J, Lasserson D, Pavord ID, Morgan S, Richards D (2021) Azithromycin versus standard care in patients with mild-to-moderate COVID-19 (ATOMIC2): An open-label, randomised trial. Lancet Respir Med 9: 1130–1140. https://doi.org/10.1016/S2213-2600(21)00263-0

Husby A, Pottegård A, Hviid A (2021) Association between inhaled corticosteroid use and COVID-19 outcomes. Pharmacoepidemiol Drug Saf 30: 1486–1492. https://doi.org/10.1002/pds.5345

Lamont T, Cousins D, Rosario C (2010) Safer treatment doses for low molecular weight heparins: Summary of a safety report from the National Patient Safety Agency. BMJ 341: 1047–1049. https://doi.org/10.1136/bmj.c5884

Laporte JR (1993) Estudios de utilización de medicamentos y de farmacovigilancia. En: Laporte JR, Tognoni G, eds. Principios de epidemiología del medicamento, 2. ed. Barcelona: Masson-Salvat, pp. 2–24.

Li J, Li Y, Yang B, Wang H, Li L (2008) Low-molecular-weight heparin treatment for acute lung injury/acute respiratory distress syndrome: A meta-analysis of randomized controlled trials. Int J Clin Exp Med 11: 414–422.

Medrano M, Mauri J, Bruscas C (2007) Tendinopatías por fluoroquinolonas. An Med Interna 24: 227–230.

Messina F, Marin E, Valerga M, Depardo R, Chediak V, Romero M, Benchetrit A, Lista N, Rodríguez A, Domínguez C, Bouzas B, Cunto E, Vaustat D, Santiso GM (2021) Infecciones fúngicas en pacientes con COVID19. ASEI 29: 6–16. https://doi.org/10.52226/revista.v29i105.49

Meza J, Quintana D, Churango J (2020) Identificación de interacciones medicamentosas de las recetas prescritas del servicio de UCI de la clínica internacional durante el periodo marzo-junio 2020 [Licenciatura]. Perú: Universidad Interamericana, pp. 71.

Plasencia, T, Aguilera R, Almaguer L (2020) Comorbilidades y gravedad clínica de la COVID-19: revisión sistemática y meta-análisis. Rev Habanera Cienc Medicas 19: 33.

Rang HP, Dale MM, Ritter JM, Moore PK (2020) Farmacología, 9a edición. Barcelona, España: Elsevier.

RECOVERY. University of Oxford (2020) Low-cost dexamethasone reduces death by up to one-third in hospitalized patients with severe respiratory complications of COVID-19. https://www.recoverytrial.net/news/low-cost-dexamethasone-reduces-death-by-up-to-one-third-in-hospitalised-patients-with-severe-respiratory-complications-of-covid-19 [Consulted 6 December 2021].

Tortosa F, Balaciano G, Carrasco G, Chávez C, García D, Montero G, Rucci P, Sanguine V (2020) Tratamiento con dexametasona en caso de infección por COVID-19: informe rápido de evaluación de tecnología sanitaria. Rev Argent Salud Publica 12: 1–8.

Valenzuela K, Espinoza A, Quispe J (2020) Mortalidad y factores pronósticos en pacientes hospitalizados por COVID-19 en la Unidad de Cuidados Intermedios de un hospital público de Lima, Perú. Horiz Med 21: e1370. https://doi.org/10.24265/horizmed.2021.v21n1.05

World Health Organization (2022) Semáforo epidemiológico, información general. https://datos.covid-19.conacyt.mx [Consulted 11 January 2022].

World Health Organization (2021a) Manejo clínico de la COVID-19. Orientaciones evolutivas. https://apps.who.int/iris/bitstream/handle/10665/340629/WHO-2019-nCoV-clinical-2021.1-spa.pdf [Consulted 6 December 2021].

World Health Organization (2021b) Declaración de la OMS: El alcohol y la COVID-19: lo que debe saber. https://coronavirus.onu.org.mx/wp-content/uploads/2020/04/SP_ALC_COVID_LONG_SHEET_11420OPS.pdf [Consulted 6 December 2021].

Ziehl EA, Córdova PM, Fernández PB, Morales FE, Villa LA (2019) Drug-drug interactions in an intensive care unit of a tertiary hospital in southern Chile: Evaluating databases agreement. J Pharm Pharmacogn Res 7(3): 184–192.

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Multi-epitope spike glycoprotein vaccine for SARS-CoV-2

Pharmaceutical Science, , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 3, pp. 445-458, May-June 2022.

DOI: https://doi.org/10.56499/jppres21.1210_10.3.445

Original Article

Development of a multi-epitope spike glycoprotein vaccine to combat SARS-CoV-2 using the bioinformatics approach

[Desarrollo de una vacuna de glicoproteína spike multiepítopo para combatir el SARS-CoV-2 utilizando el enfoque bioinformático]

Aamir Shehzad1, Christijogo Sumartono2, Jusak Nugraha3, Helen Susilowati4, Andi Yasmin Wijaya4, Hafiz Ishfaq Ahmad5, Muhammad Kashif6, Wiwiek Tyasningsih7, Fedik Abdul Rantam1,4*

1Virology and Immunology Laboratory, Division of Microbiology, Faculty of Veterinary Medicine, Airlangga University, Surabaya, East Java, 60115, Indonesia.

2Anasthesiology and Reanimation Department, Dr. Soetomo Gerneral Hospital and Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Clinical Pathology Department, Dr. Soetomo Gerneral Hospital and Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

4Research Center for Vaccine Technology and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.

5Department of Animal Breeding and Genetics, University of Veterinary and Animal Sciences, Ravi Campus, Pattoki, Punjab, Pakistan.

6Department of Biomedical Engineering, Science and Technology, Universitas Airlangga, Surabaya, Indonesia.

7Bacteriology and Mycology Laboratory, Department of Microbiology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, 60132, Indonesia.

*E-mail: fedik-a-r@fkh.unair.ac.id

Abstract

Context: The current COVID-19 pandemic has significantly impacted health and socio-economic status worldwide. The only way to combat this situation is to develop an effective vaccine and immunize people around the globe.

Aims: To construct a multi-epitope spike glycoprotein-based vaccine from the SARS-CoV-2 Surabaya isolate using a bioinformatics approach.

Methods: The spike protein was submitted to IEDB, VaxiJen, AllerTOP, and ToxinPred webservers to predict antigenic, non-allergic, non-toxic, B- and T-cell epitopes. To develop a multi-epitope vaccine, an adjuvant cholera toxin B subunit was linked to B-cell and B-cell with T-cell through EAAAK and GPGPG linkers, respectively. The designed vaccine 3D structure development, refinement, and validation were done through PHYRE2, Galaxy Refine, and RAMPAGE webservers. Moreover, the Cluspro-2.0 webserver was used for the molecular docking of the vaccine designed with TLR3. The vaccine+TLR3 complex was docked with Surfactant protein A as a control to validate the docking results. Finally, immune-simulation and in silico cloning of the vaccine were carried out by C-ImmSim webserver and SnapGene software, respectively.

Results: A multi-epitopic vaccine containing B and T-cell was developed using 392 amino acids with a molecular weight of 40825.59 Da. The docking and immunogenicity results of the vaccine met all established parameters for constructing a quality vaccine. Furthermore, the optimized sequence of the vaccine was successfully cloned in expression vector pET 28 a (+) that yielded a colon of 2724 bp.

Conclusions: The vaccine’s immunogenicity demonstrates its effectiveness against SARS-CoV-2 infection. Further confirmatory testing may therefore be performed as soon as possible in the public interest.

Keywords: in silico; public health; SARS-CoV-2; spike protein; TLR3-receptor.

Resumen

Contexto: La actual pandemia de COVID-19 ha afectado significativamente la salud y el estado socioeconómico en todo el mundo. La única forma de combatir esta situación es desarrollar una vacuna eficaz e inmunizar a las personas en todo el mundo.

Objetivos: Construir una vacuna basada en glicoproteína de pico de múltiples epítopos a partir del aislado SARS-CoV-2 Surabaya utilizando un enfoque bioinformático.

Métodos: La proteína de pico se envió a los servidores web IEDB, VaxiJen, AllerTOP y ToxinPred para predecir epítopos antigénicos, no alérgicos, no tóxicos, de células B y T. Para desarrollar una vacuna multiepítopo, se unió una subunidad B de la toxina del cólera adyuvante a la célula B y una célula B a una célula T a través de conectores EAAAK y GPGPG, respectivamente. El desarrollo, el refinamiento y la validación de la estructura 3D de la vacuna diseñada se realizaron a través de los servidores web PHYRE2, Galaxy Refine y RAMPAGE. Además, se utilizó el servidor web Cluspro-2.0 para el acoplamiento molecular de la vacuna diseñada con TLR3. El complejo vacuna + TLR3 se acopló con la proteína A del tensioactivo como control para validar los resultados del acoplamiento. Finalmente, la inmunosimulación y la clonación in silico de la vacuna se llevaron a cabo mediante el servidor web C-ImmSim y el software SnapGene, respectivamente.

Resultados: Se desarrolló una vacuna multiepitópica que contenía células B y T utilizando 392 aminoácidos con un peso molecular de 40825,59 Da. Los resultados de acoplamiento e inmunogenicidad de la vacuna cumplieron con todos los parámetros establecidos para construir una vacuna de calidad. Además, la secuencia optimizada de la vacuna se clonó con éxito en el vector de expresión pET 28 a (+) que produjo un colon de 2724 pb.

Conclusiones: La inmunogenicidad de la vacuna demuestra su eficacia contra la infección por SARS-CoV-2. Por lo tanto, se pueden realizar más pruebas de confirmación lo antes posible en interés público.

Palabras Clave: in silico; proteína de punta; receptor TLR3; salud pública; SARS-CoV-2.

This image has an empty alt attribute; its file name is jppres_pdf_free.png

Download the PDF file .

 
Citation Format: Shehzad A, Sumartono C, Nugraha J, Susilowati H, Wijaya AY, Ahmad HI, Kashif M, Tyasningsih W, Rantam FA (2022) Development of a multi-epitope spike glycoprotein vaccine to combat SARS-CoV-2 using the bioinformatics approach. J Pharm Pharmacogn Res 10(3): 445–458.https://doi.org/10.56499/jppres21.1210_10.3.445
References

Abraham Peele K, Srihansa T, Krupanidhi S, Ayyagari VS, Venkateswarulu TC (2021) Design of multi-epitope vaccine candidate against SARS-CoV-2: A in-silico study. J Biomol Struct Dyn 39(10): 3793–3801.

Ahmad B, Ashfaq UA, Rahman MU, Masoud MS, Yousaf MZ (2019) Conserved B and T cell epitopes prediction of Ebola virus glycoprotein for vaccine development: An immuno-informatics approach. Microb Pathog 132: 243–253.

Ahmad I, Ali SS, Zafar B, Hashmi HF, Shah I, Khan S, Suleman M, Khan M, Ullah S, Ali S, Khan J (2020) Development of multi-epitope subunit vaccine for protection against the norovirus’ infections based on computational vaccinology. J Biomol Struct Dyn 9: 1–12.

Ali M, Pandey RK, Khatoon N, Narula A, Mishra A, Prajapati VK (2017) Exploring dengue genome to construct a multi-epitope-based subunit vaccine by utilizing immunoinformatics approach to the battle against dengue infection. Sci Rep 7(1): 9232.

Amer H, Alqahtani AS, Alaklobi F, Altayeb J, Memish ZA (2018) Healthcare worker exposure to Middle East respiratory syndrome coronavirus (MERS-CoV): Revision of screening strategies urgently needed. Int J Infect Dis 71: 113–116.

Artimo P, Jonnalagedda M, Arnold K, Baratin D, Csardi G, De Castro E, Duvaud S, Flegel V, Fortier A, Gasteiger E, Grosdidier A (2012) ExPASy: SIB bioinformatics resource portal. Nucleic Acids Res 40(W1): W597–W603.

Arumugam S, Varamballi P (2021) In-silico design of envelope-based multi-epitope vaccine candidate against Kyasanur forest disease virus. Sci Rep 11(1): 17118.

Ashfaq UA, Ahmed B (2016) De novo structural modeling and conserved epitopes prediction of Zika virus envelop protein for vaccine development. Viral Immunol 29(7): 436–443.

Baruah V, Bose S (2020) Immunoinformatics‐aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019‐nCoV. J Med Virol 92(5): 495–500.

Chang KY, Yang JR (2013) Analysis and prediction of highly effective antiviral peptides based on random forests. PloS One 8(8): e70166.

Chukwudozie OS, Chukwuanukwu RC, Iroanya OO, Eze DM, Duru VC, Dele-Alimi TO, Kehinde BD, Bankole TT, Obi PC, Okinedo EU (2020) Attenuated subcomponent vaccine design targeting the SARS-CoV-2 nucleocapsid phosphoprotein RNA binding domain: In silico analysis. J Immunol Res 2020: 2837670.

Chukwudozie OS, Gray CM, Fagbayi TA, Chukwuanukwu RC, Oyebanji VO, Bankole TT, Adewole RA, Daniel EM (2021) Immuno-informatics design of a multimeric epitope peptide-based vaccine targeting SARS-CoV-2 spike glycoprotein. Plos One 16(3): e0248061.

Cockrell AS, Johnson JC, Moore IN, Liu DX, Bock KW, Douglas MG, Graham RL, Solomon J, Torzewski L, Bartos C, Hart R (2018) A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques. Sci Rep 8(1): 10727.

Dar HA, Waheed Y, Najmi MH, Ismail S, Hetta HF, Ali A, Muhammad K (2020) Multiepitope subunit vaccine design against COVID-19 based on the spike protein of SARS-CoV-2: An in silico analysis. J Immunol Res 2020: 8893483.

Dimitrov I, Flower DR, Doytchinova I (2013) AllerTOP-a server for in silico prediction of allergens. BMC Bioinform 14(suppl. 6): S4.

Dong R, Chu Z, Yu F, Zha Y (2020) Contriving multi-epitope subunit of vaccine for COVID-19: Immunoinformatics approaches. Front Immunol 11:1784.

Doytchinova IA, Flower DR (2007) VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinform 8(1): 4.

Gasteiger E, Hoogland C, Gattiker A, Wilkins MR, Appel RD, Bairoch A (2005) Protein identification and analysis tools on the ExPASy server. The Proteomics Protocols Handbook, pp. 571–607.

Geourjon C, Deleage G (1995) SOPMA: Significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments. Bioinform 11(6): 681–684.

Gupta S, Kapoor P, Chaudhary K, Gautam A, Kumar R, Open-Source Drug Discovery Consortium, Raghava GP (2013) In silico approach for predicting toxicity of peptides and proteins. PloS One 8(9): e73957.

Houston S, Lithgow KV, Osbak KK, Kenyon CR, Cameron CE (2018) Functional insights from proteome-wide structural modeling of Treponema pallidum subspecies pallidum, the causative agent of syphilis. BMC Struct Biol 18(1): 7.

Hui DS, Azhar EI, Kim YJ, Memish ZA, Oh MD, Zumla A (2018) Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission. Lancet Infect Dis 18(8): e217-27.

Ikai A (1980) Thermostability and aliphatic index of globular proteins. J Biochem 88(6): 1895-1898.

Indriani R (2001) Antibody response and protection of inactivated-local isolate vaccine for infectious bronchitis in laying chicken. J IImTer Vet 6(2): 134–140.

Jespersen MC, Peters B, Nielsen M, Marcatili P (2017) BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes. Nucleic Acids Res 45(W1): W24–W29.

Jyotisha, Singh S, Qureshi IA (2020) Multi-epitope vaccine against SARS-CoV-2 applying immunoinformatics and molecular dynamics simulation approaches. J Biomol Struct Dyn 6: 1–17.

Kamens J (2015) The Addgene repository: an international nonprofit plasmid and data resource. Nucleic Acids Res 43(D1): D1152–D1157.

Kathwate GH (2022) In silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike protein. Int J Pept Res Ther 28(1): 37.

Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ (2015) The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc 10(6): 845–858.

Khalil I, Omer I, Farh IZ, Mohamed HA, Elsharif HA, Mohamed AA, Awad-Elkareem MA, Salih MA (2018) Design of an epitope-based peptide vaccine against Cryptococcus neoformans. BioRxiv [Preprint]. doi: https://doi.org/10.1101/434779

Ko J, Park H, Heo L, Seok C (2012) GalaxyWEB server for protein structure prediction and refinement. Nucleic Acids Res 40(W1): W294–W297.

Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, Zhang Q, Shi X, Wang Q, Zhang L, Wang X (2020) Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 581(7807): 215–220.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W (2020) Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 395: 565–574.

Martínez-Flores D, Zepeda-Cervantes J, Cruz-Reséndiz A, Aguirre-Sampieri S, Sampieri A, Vaca L (2021) SARS-CoV-2 vaccines based on the spike glycoprotein and implications of new viral variants. Front Immunol 12: 701501.

McCartney S, Vermi W, Gilfillan S, Cella M, Murphy TL, Schreiber RD, Murphy KM, Colonna M (2009) Distinct and complementary functions of MDA5 and TLR3 in poly (I: C)-mediated activation of mouse NK cells. J Exp Med 206(13): 2967–2976.

McKee AS, Munks MW, Marrack P (2007) How do adjuvants work? Important considerations for new generation adjuvants. Immunity 27(5): 687–690.

Naveed M, Tehreem S, Arshad S, Bukhari SA, Shabbir MA, Essa R, Ali N, Zaib S, Khan A, Al-Harrasi A, Khan I (2021) Design of a novel multiple epitope-based vaccine: An immunoinformatics approach to combat SARS-CoV-2 strains. J Infect Public Health 14(7): 938–946.

O’Hagan DT, De Gregorio E (2009) The path to a successful vaccine adjuvant– ‘the long and winding road’. Drug Discov Today 14(11-12): 541–551.

Oany AR, Ahmad SA, Hossain MU, Jyoti TP (2015) Identification of highly conserved regions in L-segment of Crimean–Congo hemorrhagic fever virus and immunoinformatic prediction about potential novel vaccine. Adv Appl Bioinform Chem 8: 1–10.

Oany AR, Emran AA, Jyoti TP (2014) Design of an epitope-based peptide vaccine against spike protein of human coronavirus: an in-silico approach. Drug Des Devel Ther 8: 1139–1149.

Olvera A, Noguera-Julian M, Kilpelainen A, Romero-Martín L, Prado JG, Brander C (2020) SARS-CoV-2 consensus-sequence and matching overlapping peptides design for COVID19 immune studies and vaccine development. Vaccines 8(3): 444.

Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, Guo L, Guo R, Chen T, Hu J, Xiang Z (2020) Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 11(1): 2144.

Phan AT, Goldrath AW, Glass CK (2017) Metabolic and epigenetic coordination of T cell and macrophage immunity. Immunity 46(5): 714–729.

Poran A, Harjanto D, Malloy M, Arieta CM, Rothenberg DA, Lenkala D, van Buuren MM, Addona TA, Rooney MS, Srinivasan L, Gaynor RB (2020) Sequence-based prediction of SARS-CoV-2 vaccine targets using a mass spectrometry-based bioinformatics predictor identifies immunogenic T cell epitopes. Genome Med 12(1): 70.

Prajapat M, Sarma P, Shekhar N, Avti P, Sinha S, Kaur H, Kumar S, Bhattacharyya A, Kumar H, Bansal S, Medhi B (2020) Drug targets for corona virus: A systematic review. Indian J Pharmacol 52(1): 56–65.

Raoult D, Zumla A, Locatelli F, Ippolito G, Kroemer G (2020) Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses. Cell Stress 4(4): 66–75.

Reche PA, Fernandez-Caldas E, Flower DR, Fridkis-Hareli M, Hoshino Y (2014) Peptide-based immunotherapeutics and vaccines. J Immunol Res2014: 256784.

Sadat SM, Aghadadeghi MR, Yousefi M, Khodaei A, Larijani MS, Bahramali G (2021) Bioinformatics analysis of SARS-CoV-2 to approach an effective vaccine candidate against COVID-19. Mol Biotechnol 63(5): 389–409.

Safavi A, Kefayat A., Mahdevar E, Abiri A, Ghahremani F (2020) Exploring the out of sight antigens of SARS-CoV-2 to design a candidate multi-epitope vaccine by utilizing immunoinformatics approaches. Vaccine 38(48): 7612–7628.

Sarma P, Shekhar N, Prajapat M, Avti P, Kaur H, Kumar S, Singh S, Kumar H, Prakash A, Dhibar DP, Medhi B (2021) In-silico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain). J Biomol Struct Dyn 39(8): 2724–2732.

Shokeen K, Pandey S, Shah M, Kumar S (2020) Insight towards the effect of the multibasic cleavage site of SARS-CoV-2 spike protein on cellular proteases. BioRxiv [Preprint].doi:https://doi.org/10.1101/2020.04.25.061507.

Singh A, Thakur M, Sharma LK, Chandra K (2020) Designing a multi-epitope peptide-based vaccine against SARS-CoV-2. Sci Rep 10(1): 16219.

Srivastava S, Kamthania M, Kumar Pandey R, Kumar Saxena A, Saxena V, Kumar Singh S, Kumar Sharma R, Sharma N (2019) Design of novel multi-epitope vaccines against severe acute respiratory syndrome validated through multistage molecular interaction and dynamics. J Biomol Struct Dyn 37(16): 4345–4360.

Tahir Ul Qamar M, Rehman A, Tusleem K, Ashfaq UA, Qasim M, Zhu X, Fatima I, Shahid F, Chen LL (2020a) Designing of a next generation multi-epitope-based vaccine (MEV) against SARS-COV-2: Immunoinformatics and in silico approaches. PloS One 15(12): e0244176.

Tahir Ul Qamar M, Shokat Z, Muneer I, Ashfaq UA, Javed H, Anwar F, Bari A, Zahid B, Saari N (2020b) Multiepitope-based subunit vaccine design and evaluation against respiratory syncytial virus using reverse vaccinology approach. Vaccines 8(2): 288.

Tahir Ul Qamar MT, Bari A, Adeel MM, Maryam A, Ashfaq UA, Du X, Muneer I, Ahmad HI, Wang J (2018) Peptide vaccine against chikungunya virus: Immuno-informatics combined with molecular docking approach. J Transl Med 16(1): 298.

Tahir Ul Qamar MT, Saleem S, Ashfaq UA, Bari A, Anwar F, Alqahtani S (2019) Epitope‐based peptide vaccine design and target site depiction against Middle East Respiratory Syndrome Coronavirus: An immune-informatics study. J Transl Med 17(1): 362.

Wan Y, Shang J, Graham R, Baric RS, Li F (2020) Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS coronavirus. Virol J94(7): e00127-20.

Weiss SR, Navas-Martin S (2005) Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev 69(4): 635–664.

WHO (2021) World Health Organization. https://covid19.who.int/ [Consulted September 27, 2021].

Wu JT, Leung K, Leung GM (2020) Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: A modelling study. Lancet 395(10225): 689–697.

Yang Z, Bogdan P, Nazarian S (2021) An in silico deep learning approach to multi-epitope vaccine design: A SARS-CoV-2 case study. Sci Rep 11(1): 3238.

Zeng L, Li D, Tong W, Shi T, Ning B (2021) Biochemical features and mutations of key proteins in SARS-CoV-2 and their impacts on RNA therapeutics. Biochem Pharmacol189: 114424.

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579 (7798): 270–273.

Zhu X, Liu Q, Du L, Lu L, Jiang S (2013) Receptor-binding domain as a target for developing SARS vaccines. J Thorac Dis 5(Suppl 2): S142–S148.

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

B-cell epitopes for the development of SARS-CoV-2 vaccine

Pharmaceutical Science, , , , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 3, pp. 429-444, May-June 2022.

DOI: https://doi.org/10.56499/jppres21.1262_10.3.429

Original Article

Molecular characterization and prediction of B-cell epitopes for the development of SARS-CoV-2 vaccine through bioinformatics approach

[Caracterización molecular y predicción de epítopos de células B para el desarrollo de una vacuna contra el SARS-CoV-2 mediante un enfoque bioinformático]

Aamir Shehzad1, Martia Rani Tacharina1, Suryo Kuncorojakti2 , Hafiz Ishfaq Ahmad3, Rofiqul A’la1, Andi Yasmin Wijaya4, Wiwiek Tyasningsih5, Fedik Abdul Rantam1,4*

1Virology and Immunology Laboratory, Department of Microbiology, Faculty of Veterinary Medicine, Airlangga University, Surabaya, East Java, 60115, Indonesia.

2Division of Veterinary Anatomy, Department of Veterinary Science, Faculty of Veterinary Medicine Airlangga University, Surabaya, East Java, 60115, Indonesia.

3Department of Animal Breeding and Genetics, University of Veterinary and Animal Sciences, Lahore, Pakistan.

4Research Center for Vaccine Technology and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, East Java, 60115 Indonesia.

5Bacteriology and Mycology Laboratory, Department of Microbiology, Faculty of Veterinary Medicine, Airlangga University, Surabaya, East Java, 60132, Indonesia.

*E-mail: fedik-a-r@fkh.unair.ac.id

Abstract

Context: The SARS-CoV-2 virus is the cause of the COVID-19 pandemic, which is a severe public health crisis worldwide.Aims: To analyze the SARS-CoV-2 isolates of Surabaya and predict ORF1ab polyprotein epitopes through the bioinformatics approach for vaccine candidate development.

Methods: Three genomic sequences of Surabaya isolates were obtained from the GISAID, NCBI and PDB Gen-bank databases and MEGA-11 software were used to understand the transformations in the isolates. The IEDB and VaxiJen, AllerTop, and ToxinPred web servers were used to predict B-cell epitopes and analyze their antigenicity, non-allergenicity, non-toxicity, respectively. Moreover, these epitopes were linked by EAAAK for 3D modeling, refinement, and validation through Swiss-Model, Galaxy Refine, and RAMPAGE web tools.

Results: The Surabaya isolates, RSDS-RCVTD-UNAIR-49-A, 54-A, and 42-A, had 10, 20, and 16 mutations in nucleotides and depicted a phylogenetically close relationship to isolates of Egypt, Pakistan, and Bangladesh, respectively. A total of 71 sequential Orf1ab B-cell epitopes were predicted, and only three peptides were found to be antigenic,  non-allergenic, and non-toxic. These epitopes were linked with the EAAAK linker to develop a 3D refined and validated structure. This construct was docked with TLR-3 receptor by the Cluspro webserver and found a high affinity of ORF1ab+TLR3 due to 15 hydrogen bonds. The construct demonstrated good humoral and cellular immune responses in the C-ImmSim server, and cloning in the expression vector pET28a (+) yielded a colon of 846bp.

Conclusions: ORF1ab B-cell epitopes could be useful for developing effective vaccines to combat SARS-CoV-2 infection.

Keywords: bioinformatics; epitopes; ORF1ab polyproteins; public health; Indonesia; SARS-CoV-2.

Resumen

Contexto: El virus SARS-CoV-2 es la causa de la pandemia de COVID-19, que es una grave crisis de salud pública a nivel mundial.Objetivos: Analizar los aislamientos de SARS-CoV-2 de Surabaya y predecir los epítopos de poliproteína ORF1ab mediante el enfoque bioinformático para el desarrollo de candidatos vacunales.

Métodos: Se obtuvieron tres secuencias genómicas de aislamientos de Surabaya de las bases de datos GISAID, NCBI and PDB  Gen-bank y el software MEGA-11 para comprender las transformaciones en los aislamientos. Se utilizaron los servidores web IEDB y VaxiJen, AllerTop y ToxinPred para predecir epítopos de células B y analizar su antigenicidad, no alergenicidad y no toxicidad, respectivamente. Además, EAAAK vinculó estos epítopos para el modelado, el refinamiento y la validación en 3D a través de las herramientas web Swiss-Model, Galaxy Refine y RAMPAGE.

Resultados: Los aislamientos de Surabaya, RSDS-RCVTD-UNAIR-49-A, 54-A y 42-A, tenían 10, 20 y 16 mutaciones en nucleótidos y mostraban una relación filogenéticamente cercana con los aislamientos de Egipto, Pakistán y Bangladesh, respectivamente. Se predijeron un total de 71 epítopos de células B Orf1ab secuenciales, y solo tres péptidos resultaron ser antigénicos, no alergénicos y no tóxicos. Estos epítopos se vincularon con el enlazador EAAAK para desarrollar una estructura 3D refinada y validada. Esta construcción fue acoplada con el receptor TLR-3 por el servidor web Cluspro y encontró una alta afinidad de ORF1ab+TLR3 debido a 15 enlaces de hidrógeno. La construcción demostró buenas respuestas inmunitarias celulares y humorales en el servidor C-ImmSim, y la clonación en el vector de expresión pET28a (+) produjo un colon de 846 pb.

Conclusiones: Los epítopos de células B ORF1ab podrían ser útiles para desarrollar vacunas efectivas para combatir la infección por SARS-CoV-2.

Palabras Clave: bioinformática; epítopos; poliproteínas ORF1ab; Indonesia; salud pública; SARS-CoV-2.

This image has an empty alt attribute; its file name is jppres_pdf_free.png

Download the PDF file .

 
Citation Format: Shehzad A, Kuncorojakti S, Tacharina MR, Ahmad HI, A'la R, Wijaya AY, Tyasningsih W, Rantam FA (2022) Molecular characterization and prediction of B-cell epitopes for the development of SARS-CoV-2 vaccine through bioinformatics approach. J Pharm Pharmacogn Res 10(3): 429–444. https://doi.org/10.56499/jppres21.1262_10.3.429
References

Abraham Peele K, Srihansa T, Krupanidhi S, Ayyagari V S, Venkateswarulu TC (2021) Design of multi-epitope vaccine candidate against SARS-CoV-2: A in-silico study.J Biomol Struct Dyn 39: 3793–3801.

Adianingsih OR, Kharisma VD (2019) Study of B cell epitope conserved region of the Zika virus envelope glycoprotein to develop multi-strain vaccine. J App Pharm Sci 9: 098–103.

Ansori AN, Kusala MK, Normalina I, Indrasari S, Alamudi MY, Nidom RV, Nidom CA (2020) Immunoinformatic investigation of three structural protein genes in Indonesian SARS-CoV-2 isolates. Sys Rev Pharm 11: 422–434.

Ansori AN, Nidom RV, Kusala MK, Indrasari S, Normalina I, Nidom AN, Nidom CA (2021) Viroinformatics investigation of B-cell epitope conserved region in SARS-CoV-2 lineage B. 1.1. 7 isolates originated from Indonesia to develop vaccine candidate against COVID-19. J Pharm Pharmacogn Res 9: 766–779.

Biswas A, Bhattacharjee U, Chakrabarti AK, Tewari DN, Banu H, Dutta S (2020) Emergence of novel coronavirus and COVID-19: Whether to stay or die out? Crit Rev Microbiol 46: 182–193.

Bond CW, Leibowitz JL, Robb JA (1979) Pathogenic murine coronaviruses II. Characterization of virus-specific proteins of murine coronaviruses JHMV and A59V. Virology 94: 371–384.

Cai J, Sun W, Huang J, Gamber M, Wu J, He G (2020) Indirect virus transmission in cluster of COVID-19 cases, Wenzhou, China, 2020. Emerg Infect Dis 26: 1343–1345.

Callaway E (2020a) Making sense of coronavirus mutations. Nature 585: 174–177.

Callaway E (2020b) The coronavirus is mutating–does it matter? Nature 585: 174–178.

Castiglione F, Mantile F, De Berardinis P, Prisco A (2012) How the interval between prime and boost injection affects the immune response in a computational model of the immune system. Comput Math Methods Med 2012: 842329.

Cevik M, Kuppalli K, Kindrachuk J, Peiris M (2020) Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ 371: m3862.

Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY (2020a) Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microb Infect  9(1): 221-236.

Chan JFW, Zhang AJ, Yuan S, Poon VKM, Chan CCS, Lee ACY, Yuen KY (2020b) Simulation of the clinical and pathological manifestations of coronavirus disease 2019 (COVID-19) in a golden Syrian hamster model: implications for disease pathogenesis and transmissibility. Clin Infect Dis 71: 2428–2446.

Chukwudozie OS, Chukwuanukwu RC, Iroanya OO, Eze DM, Duru VC, Dele-Alimi TO, Okinedo EU (2020) Attenuated subcomponent vaccine design targeting the SARS-CoV-2 nucleocapsid phosphoprotein RNA binding domain: In silico analysis. J Immunol Res 2020: 2837670.

Cooper NR, Nemerow GR (1984) The role of antibody and complement in the control of viral infections. J Investig Dermatol 83: S121–S127.

Dandekar AA, Perlman S (2005) Immunopathogenesis of coronavirus infections: Implications for SARS. Nat Rev Immunol 5: 917–927.

Dhanda SK, Mahajan S, Paul S, Yan Z, Kim H, Jespersen MC, Peters B (2019) IEDB-AR: immune epitope database—analysis resource in 2019. Nucleic Acids Res 47: W502–W506.

Dong L, Tian J, He S, Zhu C, Wang J, Liu C, Yang J (2020) Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn. JAMA 323: 1846-1848.

Duffy S (2018) Why are RNA virus mutation rates so damn high? PLoS Biol16: e3000003.

Emameh RZ, Nosrati H, Taheri RA (2020) Combination of biodata mining and computational modelling in identification and characterization of ORF1ab polyprotein of SARS-CoV-2 isolated from oronasopharynx of an Iranian patient. Biol Proced Online 22: 8.

Falzone L, Musso N, Gattuso G, Bongiorno D, Palermo CI, Scalia G, Stefani S (2020) Sensitivity assessment of droplet digital PCR for SARS-CoV-2 detection. Int J Mol Med 46: 957–964.

Fitzsimmons WJ, Woods RJ, McCrone JT, Woodman A, Arnold JJ, Yennawar M, Lauring AS (2018) A speed–fidelity trade-off determines the mutation rate and virulence of an RNA virus. PLoS Biology 16: e2006459.

Fritz M, Rosolen B, Krafft E, Becquart P, Elguero E, Vratskikh O, Denolly S, Boson B, Vanhomwegen J, Gouilh MA, Kodjo A, Chirouze C, Rosolen SG, Legros V, Leroy EM (2020) High prevalence of SARS-CoV-2 antibodies in pets from COVID-19+ households. One Health 11: 100192.

Gangaev A, Ketelaars SL, Isaeva OI, Patiwael S, Dopler A, Hoefakker K, De Biasi S, Gibellini L, Mussini C, Guaraldi G, Girardis M (2020a) Identification and characterization of an immunodominant SARS-CoV-2-specific CD8 T cell response. Res Sq [Preprint] DOI: 10.21203/rs.3.rs-33197/v2

Gangaev A, Ketelaars SL, Patiwael S, Dopler A, Isaeva OI, Hoefakker K, Kvistborg P (2020b) Profound CD8 T-cell responses towards SARS-CoV-2 OFR1ab in COVID-19 patients. Res Sq [Preprint] DOI: 10.21203/rs.3.rs-33197/v1

Gao T, Gao Y, Liu X, Nie Z, Sun H, Lin K, Wang S (2021) Identification and functional analysis of the SARS-COV-2 nucleocapsid protein. BMC Microbiol 21: 58.

Geourjon C, Deleage G (1995) SOPMA: Significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments. Bioinformatics 11: 681–684.

Ghoshal B, Ghoshal B, Swift S, Tucker A (2021) Uncertainty estimation in SARS-CoV-2 B-cell epitope prediction for vaccine development. In: International Conference on Artificial Intelligence in Medicine. Springer, Cham, p. 361–366.

GISAD (2021) GISAID Database. Available from https://www.epicov.org/epi3/frontend#6d403 [Accessed July 27, 2021].

Graham RL, Sparks JS., Eckerle LD, Sims AC, Denison MR (2008) SARS coronavirus replicase proteins in pathogenesis. Virus Res 133: 88–100.

Grote A, Hiller K, Scheer M, Münch R, Nörtemann B, Hempel DC, Jahn D (2005) JCat: A novel tool to adapt codon usage of a target gene to its potential expression host. Nucleic Acids Res 33: W526–W531.

Grubaugh ND, Hanage WP, Rasmussen AL (2020) Making sense of mutation: What D614G means for the COVID-19 pandemic remains unclear. Cell 182: 794–795.

Gupta S, Kapoor P, Chaudhary K, Gautam A, Kumar R, Open Source Drug Discovery Consortium, Raghava GP (2013) In silico approach for predicting toxicity of peptides and proteins. PloS One 8: e73957.

Hachim A, Kavian N, Cohen CA, Chin AW, Chu DK, Mok CK, Tsang OT, Yeung YC, Perera RA, Poon LL, Peiris JM (2020) ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection. Nat Immunol 21: 1293–1301.

Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, Xia Y (2020) Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect 9: 1123–1130.

Harcourt J, Tamin A, Lu X, Kamili S, Sakthivel SK, Murray J, Thornburg N J (2020) Isolation and characterization of SARS-CoV-2 from the first US COVID-19 patient. BioRxiv [Preprint] DOI: 10.1101/2020.03.02.972935

Hernández‐Huerta MT, Pérez‐Campos Mayoral L, Romero Díaz C, Martínez Cruz M, Mayoral‐Andrade G, Sanchez Navarro LM, Matias‐Cervantes CA (2021) Analysis of SARS‐CoV‐2 mutations in Mexico, Belize, and isolated regions of Guatemala and its implication in the diagnosis. Med Virol 93: 2099–2114.

Horiike T (2016) An introduction to molecular phylogenetic analysis. Rev Agri Sci 4: 36-45.

Hu J, He CL, Gao Q, Zhang GJ, Cao XX, Long QX, Huang AL (2020) The D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity. BioRxiv [Preprint] DOI: 10.1101/2020.06.20.161323

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Cao B (2020a) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395: 497–506.

Huang Y, Yang C, Xu XF, Xu W, Liu SW (2020b) Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 41: 1141–1149.

Kathwate GH (2022) In silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins. Int J Pept Res Ther 28: 37.

Khailany RA, Safdar M, Ozaslan M (2020) Genomic characterization of a novel SARS-CoV-2. Gene Reports 19: 100682.

Khan MK, Zaman S, Chakraborty S, Chakravorty R, Alam MM, Bhuiyan TR, Seraj ZI (2014) In silico predicted mycobacterial epitope elicits in vitro T-cell responses. Mo.l Immunol 61: 16–22.

Khatoon N, Pandey RK, Prajapati VK (2017) Exploring leishmania secretory proteins to design B and T cell multi-epitope subunit vaccine using immunoinformatics approach. Sci Rep 7: 8285.

Kim JI (2020) New potential for healing the trauma of Maori from Brain Education. [Interview] Dr. Lily George, Director of Education, New Zealand Headquarters of ECO. IBREA Report 12: 3–7.

Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, Montefiori DC (2020) Tracking changes in SARS-CoV-2 spike: Evidence that D614G increases infectivity of the COVID-19 virus. Cell 182: 812–827.

Kumar S, Stecher G, Tamura K (2016) MEGA7: Molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33: 1870-1874.

Lau SY, Wang P, Mok BWY, Zhang AJ, Chu H, Lee ACY, Chen H (2020) Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction. EmergMicrobes Infect 9: 837–842.

Lewis DM, Leibrand S, Leibrand H (2020) A test-based strategy for safely shortening quarantine for COVID-19. MedRxiv [Preprint] DOI:10.1101/2020.11.24.20238287

Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, Wu J (2020a) Coronavirus infections and immune responses. JMed Virol 92: 424–432.

Li J, Wang H, Mao L, Yu H, Yu X, Sun Z, Wang X (2020b) Rapid genomic characterization of SARS-CoV-2 viruses from clinical specimens using nanopore sequencing. Sci Rep 10: 17492.

Liu K, Pan X, Li L, Yu F, Zheng A, Du P, Han P, Meng Y, Zhang Y, Wu L, Chen Q (2021) Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE2 in humans and other species. Cell 184(13): 3438–3451.

Mapleson D, Drou N, Swarbreck D (2015) RAMPART: A workflow management system for de novo genome assembly. Bioinformatics 31: 1824–1826.

Martin A, Nateqi J, Gruarin S, Munsch N, Abdarahmane I, Zobel M, Knapp B (2020) An artificial intelligence-based first-line defence against COVID-19: Digitally screening citizens for risks via a chatbot. Sci Rep 10: 19012.

Meng XY, Zhang HX, Mezei M, Cui M (2011) Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des 7: 146–157.

Naveed M, Tehreem S, Arshad S, Bukhari SA, Shabbir MA, Essa R, Khan I (2021) Design of a novel multiple epitope-based vaccine: An immunoinformatics approach to combat SARS-CoV-2 strains. J Infect Public Health 14: 938–946.

Nemati AS, Tafrihi M, Sheikhi F, Tabari AR, Haditabar A (2021) Designing a new multi epitope-based vaccine against COVID-19 disease: An immunoinformatic study based on reverse vaccinology approach. Res Sq [Preprint] DOI: 10.21203/rs.3.rs-206270/v1

Oany AR, Emran AA, Jyoti TP (2014) Design of an epitope-based peptide vaccine against spike protein of human coronavirus: an in silico approach. Drug Des Devel Ther 8: 1139.

Ozono S, Zhang Y, Ode H, Seng TT, Imai K, Miyoshi K, Tokunaga K (2021) Naturally mutated spike proteins of SARS-CoV-2 variants show differential levels of cell entry. Nat Commun 12:848.

Pandey RK, Bhatt TK, Prajapati VK (2018) Novel immunoinformatics approaches to design multi-epitope subunit vaccine for malaria by investigating anopheles salivary protein. Sci Rep 8: 1125.

Park WB, Kwon NJ, Choi SJ, Kang CK, Choe PG, Kim JY, Oh MD (2020) Virus isolation from the first patient with SARS-CoV-2 in Korea. J Korean Med Sci 35: 10–14.

Rapin N, Lund O, Bernaschi M, Castiglione F (2010) Computational immunology meets bioinformatics: the use of prediction tools for molecular binding in the simulation of the immune system. PloS One 5: e9862.

Safavi A, Kefayat A, Mahdevar E, Abiri A, Ghahremani F (2020) Exploring the out of sight antigens of SARS-CoV-2 to design a candidate multi-epitope vaccine by utilizing immunoinformatics approaches. Vaccine 38: 7612–7628.

Saitou N, Nei M (1987) The neighbor-joining method: A new method for reconstructing phylogenetic trees. Mol Biol Evol 4: 406–425.

Sen Gupta PS, Biswal S, Singha D, Rana MK (2021) Binding insight of clinically oriented drug famotidine with the identified potential target of SARS-CoV-2. J Biomol Struct Dyn 39: 5327–5333.

Siegrist CA (2008) Vaccine Immunology. Vaccines. SaundersElsevier, p. 17–36.

Singh A, Thakur M, Sharma LK, Chandra K (2020) Designing a multi-epitope peptide based vaccine against SARS-CoV-2. Sci Rep 10: 16219.

Tahir ul Qamar M, Shahid F, Aslam S, Ashfaq UA, Aslam S, Fatima I, Chen LL (2020) Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2. Infect DisPoverty 9: 132.

Tamura K, Nei M, Kumar S (2004) Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci U S A 101: 11030–11035.

Tang T, Bidon M, Jaimes JA, Whittaker GR, Daniel S (2020) Coronavirus membrane fusion mechanism offers a potential target for antiviral development. Antivir Res 178: 104792.

Valencia I, Peiró C, Lorenzo Ó, Sánchez-Ferrer CF, Eckel J, Romacho T (2020) DPP4 and ACE2 in diabetes and COVID-19: therapeutic targets for cardiovascular complications? Front Pharmacol 11: 1161.

Voloch CM, da Silva Francisco Jr R, de Almeida LG, Cardoso CC, Brustolini OJ, Gerber AL, de Vasconcelos ATR (2021) Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil. Virol J 95: e00119-21.

Watanabe Y, Allen JD, Wrapp D, McLellan JS, Crispin M (2020) Site-specific glycan analysis of the SARS-CoV-2 spike. Science 369: 330–333.

Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Schwede T (2018) SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res 46: W296–W303.

Weisblum Y, Schmidt F, Zhang F, DaSilva J, Poston D, Lorenzi JC, Bieniasz PD (2020) Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife 9: e61312.

Weiss SR, Navas-Martin S (2005) Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev 69: 635–664.

WHO (2020a) World Health Organization. Naming the coronavirus disease (COVID-19) and the virus that causes it. Available at: https://www. who.int/emergencies/diseases/novel-coronavirus-2019/technicalguidance/naming-the-coronavirus-disease-(covid-2019)-and-thevirus-that-causes-it. [Accessed 2 March, 2020].

WHO (2020b) World Health Organization. Coronavirus disease 2019 (COVID-19): situation report, 32. Available at: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200221-sitrep-32-covid-19.pdf [Accessed January 05, 2022].

WHO (2021) World Health Organization. Coronavirus disease. Available from https://covid19.who.int/ [Accessed August 27, 2021].

Yadav V, Rajput M, Diwakar RP, Kumar R (2020) An Overview on transmission of diseases in special reference to COVID-19 and potential Tar-gets to control this pandemic. J Adv Microbiol Res 4: 015.

Zhang J, Zeng H, Gu J, Li H, Zheng L, Zou Q (2020) Progress and prospects on vaccine development against SARS-CoV-2. Vaccines 8: 153.

Zhang Y, Chen Y, Li Y, Huang F, Luo B, Yuan Y, Xia B, Ma X, Yang T, Yu F, Liu J (2021) The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι. Proc Natl Acad Sci U S A 118: e2024202118.

Zheng YY, Ma YT, Zhang JY, Xie X (2020) COVID-19 and the cardiovascular system. Nat Rev Cardiol 17: 259–260.

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579: 270–273.

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P (2020) A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 382: 727–733.

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Roselle flower for immunomodulatory adjuvant therapy in COVID-19

Pharmaceutical Science, , , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 3, pp. 418-428, May-June 2022

DOI: https://doi.org/10.56499/jppres21.1316_10.3.418

Original Article

Anthocyanin, tartaric acid, ascorbic acid of roselle flower (Hibiscus sabdariffa L.) for immunomodulatory adjuvant therapy in oral manifestation coronavirus disease-19: An immunoinformatic approach

[Antocianina, ácido tartárico, ácido ascórbico de flor de Jamaica (Hibiscus sabdariffa L.) para la terapia adyuvante inmunomoduladora en la manifestación oral de la enfermedad por coronavirus-19: Un enfoque inmunoinformático]

Nastiti Faradilla Ramadhani1, Alexander Patera Nugraha1,2*, Desintya Rahmadhani3, Martining Shoffa Puspitaningrum3, Yuniar Rizqianti3, Viol Dhea Kharisma4, Tengku Natasha Eleena binti Tengku Ahmad Noor5, Rini Devijanti Ridwan6, Diah Savitri Ernawati7, Albertus Putera Nugraha8

1Graduate Student of Dental Health Science, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

2Department of Orthodontic, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

4Graduate Student of Biology Science, Department of Biology, Faculty of Mathematics and Natural Science, Universitas Brawijaya, Malang, Indonesia

5Military Dental Officer of Royal Medical and Dental Corps, Malaysian Armed Forces, Indonesia.

6Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

7Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

8Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

*E-mail: alexander.patera.nugraha@fkg.unair.ac.id

Abstract

Context: Oral manifestations that arose from COVID-19 infection often causes morbidity and systemic drug administration is less effective. Roselle flower (Hibiscus sabdariffa) is one of the plants that is often used in infusion as it gives health benefits. Hence, H. sabdariffa may benefit from adjuvant therapy to treat oral manifestation due to COVID-19.

Aims: To investigate the potential of H. sabdariffa anthocyanins, tartaric acid, and ascorbic acid chemical compounds as antiviral, anti-inflammatory, antioxidant, and increasing tissue regeneration in oral manifestation due to COVID-19 infection in silico.

Methods: Chemical compounds consisted of anthocyanins, (+)-tartaric acid, and ascorbic acid beside target proteins consisted of ACE2-spike, Foxp3, IL-10, IL6, IL1β, VEGF, FGF-2, HSP70, TNFR and MDA-ovalbumin were obtained from the database, ligand samples were selected through absorption, distribution, metabolism, excretion and toxicology analysis, then molecular docking simulations, identification of protein-ligand interactions, and 3D visualization were performed.

Results: Anthocyanins, tartaric acid, and ascorbic acid are the active compounds in H. sabdariffa, which act as antioxidants. The activity of anthocyanin compounds is higher than other compounds through value binding affinity, which is more negative and binds to specific domains of target proteins by forming weak binding interactions that play a role in biological responses. Anthocyanins have the most negative binding energy compared to tartaric-acid and ascorbic acid.

Conclusions: Anthocyanins act as antioxidants; this mechanism increases heat shock protein-70 (HSP70), which may play an important role in increasing wound regeneration of oral manifestation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as documented in silico.

Keywords: COVID-19; dentistry; Hibiscus sabdariffa; infectious disease; medicine.

Resumen

Contexto: Las manifestaciones orales derivadas de la infección por COVID-19 suelen causar morbilidad y la administración sistémica de fármacos es menos efectiva. La flor de Jamaica (Hibiscus sabdariffa) es una de las plantas que se suele utilizar en infusión ya que aporta beneficios para la salud. Por lo tanto, H. sabdariffa puede beneficiarse de la terapia adyuvante para tratar las manifestaciones orales debido a COVID-19.

Objetivos: Investigar el potencial de los compuestos químicos de H. sabdariffa, como antocianinas, ácido tartárico y ácido ascórbico como antivirales, antiinflamatorios, antioxidantes y el aumento de la regeneración de tejidos en la manifestación oral debido a la infección por COVID-19 a través de un enfoque inmunoinformático, un estudio in silico.

Métodos: Antocianinas, ácido tartárico y ácido ascórbico, además de proteínas diana como ACE2-spike, Foxp3, IL-10, IL6, IL1β, VEGF, FGF-2, HSP70, TNFR y MDA-ovoalbúmina, se obtuvieron de la base de datos, las muestras de ligando se seleccionaron mediante análisis de absorción, distribución, metabolismo, excreción y toxicología, luego se realizaron simulaciones de acoplamiento molecular, identificación de interacciones proteína-ligando y visualización 3D.

Resultados: Las antocianinas, el ácido tartárico y el ácido ascórbico son los compuestos activos de H. sabdariffa que actúan como antioxidantes. La actividad de los compuestos de antocianina es mayor que la de otros compuestos a través de una afinidad de unión de valor que es más negativa y se une a dominios específicos de proteínas diana formando interacciones de unión débiles que desempeñan un papel en las respuestas biológicas. Las antocianinas tienen la energía de unión más negativa en comparación con el ácido tartárico y el ácido ascórbico.

Conclusiones: Las antocianinas actúan como antioxidantes; este mecanismo aumenta la proteína de choque térmico-70 (HSP70), que puede desempeñar un papel importante en el aumento de la regeneración de heridas de la manifestación oral en el síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2) como se documenta in silico.

Palabras Clave: COVID-19; enfermedad infecciosa; Hibiscus sabdariffa; medicamento; odontología.

This image has an empty alt attribute; its file name is jppres_pdf_free.png

Download the PDF file .

 
Citation Format: Ramadhani NF, Nugraha AP, Rahmadani D, Puspitaningrum MS, Rizqianti Y, Kharisma VD, Noor TNEBTA, Ridwan RD, Ernawati DS, Nugraha AP (2022) Anthocyanin, tartaric acid, ascorbic acid of roselle flower (Hibiscus sabdariffa L.) for immunomodulatory adjuvant therapy in oral manifestation coronavirus disease-19: An immunoinformatic approach. J Pharm Pharmacogn Res 10(3): 418–428. https://doi.org/10.56499/jppres21.1316_10.3.418
References

Al-Snafi AE (2016) Pharmacological importance of Clitoria ternatea–A review. IOSR J Pharm 6(3): 68–83.

Amorim Dos Santos J, Normando AGC, Carvalho da Silva RL, De Paula RM, Cembranel AC, Santos-Silva AR, Guerra ENS (2020) Oral mucosal lesions in a COVID-19 patient: New signs or secondary manifestations? Int J Infect Dis 97: 326–328.

Arrigoni O, De Tullio MC (2002) Ascorbic acid: Much more than just an antioxidant. Biochim Biophys Acta 1569(1-3): 1–9.

Atiqi S, Hooijberg F, Loeff FC, Rispens T, Wolbink GJ (2020) Immunogenicity of TNF-inhibitors. Front Immunol 11: 312.

Babich O, Sukhikh S, Prosekov A, Asyakina L, Ivanova S (2020) Medicinal plants to strengthen immunity during a pandemic. Pharmaceuticals 13(10): 313.

Bell LCK, Meydan C, Kim J, Foox J, Butler D, Mason CE, Shapira SD, Noursadeghi M, Pollara G (2021) Transcriptional response modules characterize IL-1β and IL-6 activity in COVID-19. iScience 24(1): 101896.

Carvajal-Zarrabal O, Barradas-Dermitz DM, Orta-Flores Z, Hayward-Jones PM, Nolasco-Hipólito C, Aguilar-Uscanga MG, Miranda-Medina A, Bujang KB (2012) Hibiscus sabdariffa L, roselle calyx, from ethnobotany to pharmacology. J Exp Pharmacol 4: 25–39.

Coomes EA, Haghbayan H (2020) Interleukin-6 in Covid-19: A systematic review and meta-analysis. Rev Med Virol 30(6): 1–9.

Danladi J, Sabir H (2021) Innate immunity, inflammation activation and heat-shock protein in COVID-19 pathogenesis. J Neuroimmunol 358: 577632.

Dewi AMC, Dagradi EM, Wibowo P (2021) The effect of high dose vitamin C (ascorbic acid) on pro-inflammatory cytokines in COVID-19. Med Health Sci J 5(1): 46–50.

Díaz Rodríguez M, Jimenez Romera A, Villarroel M (2020) Oral manifestations associated with COVID‐19. Oral Dis DOI: 10.1111/odi.13555

Diomede F, Marconi GD, Fonticoli L, Pizzicanella J, Merciaro I, Bramanti P, Mazzon E, Trubiani O (2020) Functional relationship between osteogenesis and angiogenesis in tissue regeneration. Int J Mol Sci 21(9): 3242.

Fakeye T (2008) Toxicity and immunomodulatory activity of fractions of Hibiscus sabdariffa Linn (family Malvaceae) in animal models. Afr J Tradit Complement Altern Med 5(4): 394–398.

Galvan-Pena S, Leon J, Chowdhary K, Michelson DA, Vijaykumar B, Yang L, Magnuson A, Manickas-Hill Z, Piechocka-Trocha A, Worrall DP, Hall KE, Ghebremichael M, Walker BD, Li JZ, Yu XG, Mathis D, Benoist C (2020) Profound Treg perturbations correlate with COVID-19 severity. bioRxiv [Preprint]. 12(11): 416180.

Gani MA, Nurhan AD, Maulana S, Siswodihardjo S, Shinta DW, Khotib J (2021) Structure-based virtual screening of bioactive compounds from Indonesian medical plants against severe acute respiratory syndrome coronavirus-2. J Adv Pharm Technol Res 12: 120–126.

Gollen B, Mehla J, Gupta P (2018) Clitoria ternatea Linn: A herb with potential pharmacological activities: Future prospects as therapeutic herbal medicine. J Pharma Reports 3(1): 1000141.

Haider T, Simader E, Glück O, Ankersmit HJ, Heinz T, Hajdu S, Negrin LL (2019) Systemic release of heat-shock protein 27 and 70 following severe trauma. Sci Rep 9(1): 9595.

Heck TG, Ludwig MS, Frizzo MN, Rasia-Filho AA, Homem de Bittencourt PI (2020) Suppressed anti-inflammatory heat shock response in high-risk COVID-19 patients: Lessons from basic research (inclusive bats), light on conceivable therapies. Clin Sci (Lond) 134(15): 1991–2017.

Iranmanesh B, Khalili M, Amiri R, Zartab H, Aflatoonian M (2021) Oral manifestations of COVID‐19 disease: A review article. Dermatol Ther 34(1): e14578.

Izquierdo-Vega JA, Arteaga-Badillo DA, Sánchez-Gutiérrez M, Morales-González JA, Vargas-Mendoza N, Gómez-Aldapa CA, Castro-Rosas J, Delgado-Olivares L, Madrigal-Bujaidar E, Madrigal-Santillán E (2020) Organic acids from roselle (Hibiscus sabdariffa L.)—A brief review of its pharmacological effects. Biomedicines 8(5): 100.

Jiang XW, Zhang Y, Zhang H, Lu K, Yang SK, Sun GL (2013) Double-blind, randomized, controlled clinical trial of the effects of diosmectite and basic fibroblast growth factor paste on the treatment of minor recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Radiol 116(5): 570–575.

Khandia R, Munjal AK, Iqbal HMN, Dhama K (2017) Heat shock proteins: Therapeutic perspectives in inflammatory disorders. Recent Pat Inflamm Allergy Drug Discov 10(2): 94–104.

Kharisma VD, Ansori ANM, Widyananda MH, Utami SL, Nugraha AP (2020) Molecular simulation: The potency of conserved region on E6 HPV-16 as a binding target of black tea compounds against cervical cancer. Biochem Cell Arch 20(Suppl 1): 2795–2802.

Kharisma VD, Widyananda MH, Ansori ANM, Nege A, Naw SW, Nugraha AP (2021) Tea catechin as antiviral agent via apoptosis agonist and triple inhibitor mechanism against HIV-1 infection: A bioinformatics approach. J Pharm Pharmacogn Res 9(4): 435–445.

Li S, Zhang Y, Guan Z, Li H, Ye M, Chen X, Shen J, Zhou Y, Shi ZL, Zhou P, Peng K (2020) SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation. Signal Transduct Target Ther 5(1): 235.

López-Collazo E, Avendaño-Ortiz J, Martín-Quirós A, Aguirre LA (2020) Immune response and COVID-19: A mirror image of sepsis. Int J Biol Sci 16(14): 2479–2489.

Luo XH, Zhu Y, Mao J, Du RC (2021) T cell immunobiology and cytokine storm of COVID-19. Scand J Immunol 93(3): e12989.

Luqman A, Kharisma VD, Ruiz RA, Götz F (2020) In silico and in vitro study of trace amines (TA) and dopamine (DOP) interaction with human alpha1-adrenergic receptor and the bacterial adrenergic receptor QseC. Cell Physiol Biochem 54: 888–898.

Marpaung A (2020) Tinjauan manfaat bunga telang (Clitoria ternatea L.) bagi kesehatan manusia. J Funct Food Nutraceutical 1(2): 47–69.

Mehri F, Rahbar AH, Ghane ET, Souri B, Esfahani M (2021) Changes in oxidative markers in COVID-19 patients. Arch Med Res 52(8): 843–849.

Mishra N, Tandon VL, Gupta R (2012) Immunomodulation by Hibiscus rosa-sinensis: Effect on the humoral and cellular immune response of Mus musculus. Pak J Biol Sci 15(6): 277–283.

Plum SM, Vu HA, Mercer B, Fogler WE, Fortier AH (2004) Generation of a specific immunological response to FGF-2 does not affect wound healing or reproduction. Immunopharmacol Immunotoxicol 26(1): 29–41.

Putra WE, Kharisma VD, Susanto H (2020) The exploration of medicinal plants’ phytochemical compounds as potential inhibitor against human α-3 nicotinic acetylcholine receptors: The insight from computational study. AIP Conf Proc 2231(1): 040078.

Reang J, Sharma PC, Thakur VK, Majeed J (2021) Understanding the therapeutic potential of ascorbic acid in the battle to overcome cancer. Biomolecules 11(8): 1130.

Sari F, Nurkhasanah, Bachri MS (2016) Acute toxicity test of rosella (Hibiscus sabdariffa L.) calyx ethanolic extract on Sprague Dawley rats. Trad Med J 21: 12–18.

Shruthi VH, Ramachandra CT, Nidoni U, Hiregoudar S, Naik N, Kurubar AR (2016) Roselle (Hibiscus sabdariffa L.) as a source of natural colour: A review. Plant Arch 16(2): 515–522.

Smadja DM, Philippe A, Bory O, Gendron N, Beauvais A, Gruest M, Peron N, Khider L, Guerin CL, Goudot G, Levavasseur F, Duchemin J, Pene F, Cheurfa C, Szwebel TA, Sourdeau E, Planquette B, Hauw-Berlemont C, Hermann B, Gaussem P, Samama CM, Mirault T, Terrier B, Sanchez O, Rance B, Fontenay M, Diehl JL, Chocron R (2021) Placental growth factor level in plasma predicts COVID-19 severity and in-hospital mortality. J Thromb Haemost 19(7): 1823–1830.

Sokol CL, Luster AD (2015) The chemokine system in innate immunity. Cold Spring Harb Perspect Biol 7(5): a016303.

Susanto H, Kharisma VD, Listyorini D, Taufiq A (2018) Effectivity of black tea polyphenol in adipogenesis related IGF-1 and its receptor pathway through in silico based study. J Phys Conf Ser 1093 (1): 012037.

Syahrana NA, Akrom A, Darmawan E (2017) Efek serbuk bunga rosella merah (Hibiscus sabdariffa L.) terhadap ekspresi IL-10 pada sukarelawan sehat. Indones J Pharm Pharm Sci 4(1): 1–5.

Umeoguaju FU, Ephraim-Emmanuel BC, Uba JO, Bekibele GE, Chigozie N, Orisakwe OE (2021) Immunomodulatory and mechanistic considerations of Hibiscus sabdariffa (HS) in dysfunctional immune responses: A systematic review. Front Immunol 12: 550670.

Velavan TP, Meyer CG (2020) The COVID‐19 epidemic. Trop Med Int Health 25(3): 278.

Vieira AR (2021) Oral manifestations in coronavirus disease 2019 (COVID-19). Oral Dis 27(3): 770.

Widyananda MH, Pratama SK, Samoedra RS, Sari FN, Kharisma VD, Ansori ANM, Yulanda A (2021) Molecular docking study of sea urchin (Arbacia lixula) peptides as multi-target inhibitor for non-small cell lung cancer (NSCLC) associated proteins. J Pharm Pharmacogn Res 9(4): 484–496

WHO (2021) World Health Organization. https://covid19.who.int/table [Accessed online on: 19 March 2021]

Yalçin B, Arda N, Tezel GG, Erman M, Alli N (2006) Expressions of vascular endothelial growth factor and CD34 in oral aphthous lesions of Behçet’s disease. Anal Quant Cytol Histol 28(6): 303–306.

Zhang JM, An J (2007) Cytokines, inflammation, and pain. Int Anesthesiol Clin 45(2): 27–37.

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Phytotherapy against COVID-19 and risks of intoxication

Pharmaceutical Science, , , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 3, pp. 357-386, May-June 2022.

DOI: https://doi.org/10.56499/jppres21.1257_10.3.357

Original Article

Phytotherapy in response to COVID-19 and risks of intoxication: A field study in the city of Meknes (Morocco)

[Fitoterapia en respuesta al COVID-19 y riesgos de intoxicación: un estudio de campo en la ciudad de Meknes (Marruecos)]

Mariame Najem*, Jamal Ibijbijen, Laila Nassiri

Environment and Valorisation of Microbial and Plant Resources Unit, Faculty of Sciences, Moulay Ismail University of Meknes, P.O.B: 11201 Meknes, Morocco.

*E-mail: ma.najem@edu.umi.ac.ma, mariamenajem@gmail.com

Abstract

Context: The contagious global pandemic of coronavirus 2019 (COVID-19) has prompted many Moroccans to turn to traditional phytoremedies.

Aims: To highlight the ethnopharmacological information and the risks of intoxication related to the use of herbal medicine to combat COVID-19.

Methods: Through a semi-structured questionnaire and using the “Free listing” technique, an ethnobotanical survey was conducted among 36 herbalists of the Meknes prefecture to collect ethnopharmacological data on species used in the fight against COVID-19. Then, many databases were used to document their pharmacological and toxicological activities.

Results: A total of 36 species in 22 families were reported to be used to prepare traditional recipes against COVID-19. According to the relative frequency index of citation, the species Artemisia herba-alba Asso, Eucalyptus globulus Labill, Syzygium aromaticum (L.) Merr. & L.M. Perry, Citrus limon (L.) Osbeck, and Zingiber officinale Roscoe. were recommended by all respondents and recorded the highest usage values. Based on the value of the plant parts index, leaves were the most used part (PPV = 0.37). Most of the remedies were prepared as infusions and administered orally. The bibliographic research revealed that the plants used have several biological activities and are frequently used to treat respiratory diseases. However, some of them have been reported to be toxic.

Conclusions: Recommended species are endowed with innumerable biological activities. They can be a promising alternative to combat COVID-19. However, their toxic effects require pharmacotoxicological studies to ensure the safety and efficacy of these natural remedies.

Keywords: COVID-19; ethnobotany; herbalism; Morocco; Meknes; phytotherapy; toxicity.

Resumen

Contexto: La contagiosa pandemia mundial del coronavirus 2019 (COVID-19) ha llevado a muchos marroquíes a recurrir a los fitorremedios tradicionales.

Objetivos: Resaltar la información etnofarmacológica y los riesgos de intoxicación relacionados con el uso de fitoterápicos para combatir el COVID-19.

Métodos: A través de un cuestionario semiestructurado y utilizando la técnica de “Listado Libre”, se realizó un relevamiento etnobotánico entre 36 herbolarios de la prefectura de Meknes para recolectar datos etnofarmacológicos sobre especies utilizadas en la lucha contra COVID-19. Luego, se utilizaron muchas bases de datos para documentar sus actividades farmacológicas y toxicológicas.

Resultados: Se informó que un total de 36 especies en 22 familias se utilizaron en la preparación de recetas tradicionales contra COVID-19. Según el índice de frecuencia relativa de citación, las especies Artemisia herba-alba Asso, Eucalyptus globulus Labill, Syzygium aromaticum (L.) Merr. & L.M. Perry, Citrus limon (L.) Osbeck y Zingiber officinale Roscoe. son recomendados por todos los encuestados y registró los valores de uso más altos. Sobre la base del índice del valor de las partes de la planta, las hojas son la parte más utilizada (VPP = 0,37). La mayoría de los remedios se prepararon como infusiones y se administraron por vía oral. La investigación bibliográfica reveló que las plantas utilizadas tienen varias actividades biológicas y se utilizan con frecuencia en el tratamiento de enfermedades respiratorias. Sin embargo, se ha informado que algunos de ellos son tóxicos.

Conclusiones: Las especies recomendadas están dotadas de innumerables actividades biológicas, pueden ser una alternativa prometedora para combatir el COVID-19. Sin embargo, sus efectos tóxicos requieren estudios farmacotoxicológicos para garantizar la seguridad y eficacia de estos remedios naturales.

Palabras Clave: COVID-19; etnobotánica; fitoterapia; herboristería; Marruecos; Meknes; toxicidad.

This image has an empty alt attribute; its file name is jppres_pdf_free.png

Download the PDF file .

 
Citation Format: Najem M, Ibijbijen J, Nassiri L (2022) Phytotherapy in response to COVID-19 and risks of intoxication: A field study in the city of Meknes (Morocco). J Pharm Pharmacogn Res 10(3): 357–386. https://doi.org/10.56499/jppres21.1257_10.3.357
References

Aanouz I, Belhassan A, El-Khatabi K, Lakhlifi T, El-Ldrissi M, Bouachrine M (2020) Moroccan medicinal plants as inhibitors of COVID-19: Computational investigations. J Biomol Struct Dyn 39(8): 2971–2979.

Abdossi V, Moghaddam EY, Hadipanah A (2015) Chemical composition of Eucalyptus globulus grown in Iran. Biol Forum 7: 322–324.

Abdoul-Azize S (2016) Potential benefits of jujube (Zizyphus lotus L.) bioactive compounds for nutrition and health. J Nutr Metab 2016: 2867470.

Abdul-Jalil TZ, Saour KY, Nasser AA (2010) Phytochemical study of some flavonoids present in the fruits of two Ammi L. species wildly grown in Iraq. J Pharm Sci 19: 48–57.

Adam SE (1999) Effects of various levels of dietary Lepidium sativum L. seeds in rats. Am J Chin Med 27: 397–405.

Adekenov SM (1995) Sesquiterpene lactones from plants of the family Asteraceae in the Kazakhstan flora and their biological activity. Chem Nat Compd 31: 21–25.

Adhikari B, Marasini BP, Rayamajhee B, Bhattarai BR, Lamichhane G, Khadayat K, Adhikari A, Khanal S, Parajuli N (2020) Potential roles of medicinal plants for the treatment of viral diseases focusing on COVID‐19: A review. Phytother Res 35(3): 1298–1312.

Agyare C, Appiah T, Boakye YD, Apenteng JA (2017) Petroselinum crispum: A Review. Medicinal Spices and Vegetables from Africa 25: 527–547.

Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F (2013) A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed 3: 337–352.

Ahmadipour S, Ahmadipour S, Mohsenzadeh A, Asadi-Samani M (2016) The importance of some native medicinal plants of Iran effective on gastrointestinal disorders in children: A review. Der Pharm Lett 8: 61–66.

Alamgeer, Younis W, Asif H, Sharif A, Riaz H, Bukhari IA, Assiri AM (2018) Traditional medicinal plants used for respiratory disorders in Pakistan: A review of the ethno-medicinal and pharmacological evidence. Chin Med 13: 48.

Al-Ashban RM, Abou-Shaaban RR, Shah AH (2010) Toxicity studies on Trigonella foenum-graecum L. seeds used in spices and as a traditional remedy for diabetes. Orient Pharm Exp Med 10: 66–78.

Al-Farwachi MI, Rhaymah MS, Al-Badrani BA (2008) Acute toxicity of Nerium oleander aqueous leaf extract in rabbits. Iraqi J Vet Sci 22: 1–4.

Al-Hizab FA, Hussein YA, Hasseeb MM, Barakat SE, Moqbel MS (2018) Toxico-pathological studies of Foeniculum vulgare plant in Mice. Open J Pathol 8: 123–131.

Alison J, Paul D (2008) Toxicologie d’urgence. 1ère édition Elsevier/Masson.

Al-Maqtari MAA, Alghalibi SM, Alhamzy EH (2011) Chemical composition and antimicrobial activity of essential oil of Thymus vulgaris from Yemen. Turk J Biochem 36: 342–349.

Al-Shoubaki R, Ahmed AKL, Sheikh I, Shaheen F (2020) Khella induced nephropathy: A case report and review of literature. Urol Nephrol Open Access J 8: 62–64.

Al-Snafi AE (2016) Medical importance of Anthemis nobilis (Chamaemelum nobile) – A review. Asian J Pharm Sci Technol 6: 89–95.

Amin JN, Murad A, Motasem AM, Ibrahem SR, Ass’ad JM, Ayed AM (2015) Phytochemical screening and in-vitro evaluation of antioxidant and antimicrobial activities of the entire Khella plant (Ammi visnaga L.) a member of palestinian flora. Int J Pharmacogn Phytochem Res 7: 137–143.

Amole O, Izegbu M (2005) Chronic toxicity of Chenopodium ambrosioides in rats. Biomed Res 16: 111–113.

Andrade JM, Faustino C, Garcia C, Ladeiras D, Reis CP, Rijo P (2018) Rosmarinus officinalis L.: An update review of its phytochemistry and biological activity. Future Sci OA 4(4): FSO283.

Anlar HG, Bacanli M (2020) Chapter 35 – Thymoquinone: The active compound of black seed (Nigella sativa). In Pathology. Preedy VR ed. Academic Press, pp. 369–378.

Anyinam C (1995) Ecology and ethnomedicine: Exploring links between current environmental crisis and indigenous medical practices. Soc Sci Med 40: 321–329.

Aouadhi S (2010) Atlas des risques de la phytothérapie rationnelle à l’étude de 57 plantes recommandées par les herboristes. faculté de médecine de Tunis, Tunis.

Araee M, Norouzi M, Habibi G, Sheikhvatan M (2009) Toxicity of Trigonella foenum graecum (fenugreek) in bone marrow cell proliferation in rat. Pak J Pharm Sci 22: 126–130.

Asadi-Samani M, Bahmani M, Rafieian-Kopaei M (2014) The chemical composition, botanical characteristic and biological activities of Borago officinalis: A review. Asian Pac J Trop Dis 7: S22–S28.

Awad AD, Khuon OS, Ali NA (2006) Spasmoltic activity of Ammi visnaga seeds on isolated rabbit jejunum. Basrah J Sci (B) 24: 47–58.

Bachiri L, Labazi N, Daoudi A, Ibijbijen J, Nassiri L, Echchegadda G, Et Mokhtari F (2015) Etude ethnobotanique de quelques lavandes marocaines spontanées. Int J Biol Chem Sci 9: 1308–1318.

Badgujar SB, Patel VV, Bandivdekar AH, Mahajan RT (2014) Traditional uses, phytochemistry and pharmacology of Ficus carica: A review. Pharm Biol 52: 1487–1503.

Bakkali H, Ababou K, Nassim Sabah T, Moussaoui A, Ennouhi A, Fouadi FZ, Siah S, Ihrai H (2010) Les brulures chimiques par le laurier rose. Ann. Burn Fire Disasters 23: 128–130.

Baregama C, Goyal A (2019) Phytoconstituents, pharmacological activity, and medicinal use of Lepidium sativum Linn.: A review. Asian J Pharm Clin Res 12: 45–50.

Bar-On YM, Flamholz A, Phillips R, Milo R (2020) SARS-CoV-2 (COVID-19) by the numbers. Elife 9: e57309.

Bary K, El Amraoui B (2020) Moroccan traditional medicine for the prevention and relief of corona virus COVID-19 symtomes. J Appl Sci Envir Stud 3: 199–208.

Bellakhdar J (1997) La pharmacopée marocaine traditionnelle, médecine arabe ancienne et savoirs populaires. Editions Le Fennec, Ibis Press, Casablanca, Maroc.

Beltagy AM, Beltagy DM (2015) Chemical composition of Ammi visnaga L. and new cytotoxic activity of its constituents khellin and visnagin. J Pharm Sci Res 7: 285–291.

Bencheraiet R, Kherrab H, Kabouche A, Kabouche Z, Jay M (2011) Flavonols and antioxidant activity of Ammi visnaga L. (Apiaceae). Rec Nat Prod 5: 52–55.

Benítez GC, González-Tejero MR, Molero-Mesa J (2010) Pharmaceutical ethnobotany in the western part of Granada province (southern Spain): Ethnopharmacological synthesis. J Ethnopharmacol 129: 87–105.

Bhat JA, Kumar M, Bussmann RW (2013) Ecological status and traditional knowledge of medicinal plants in Kedarnath Wildlife Sanctuary of Garhwal Himalaya, India. J Ethnobiol Ethnomed 9: 1.

Bone K, Mills S (2013) Principles and Practice of Phytotherapy: Modern Herbal Medicine. 2nd Edition. Elsevier Health Sciences.

Bouchentouf S, Missoum N (2020) Identification of compounds from Nigella sativa as new potential inhibitors of 2019 novel corona virus (Covid-19): Molecular docking study. ChemRxiv. DOI: 10.26434/chemrxiv.12055716.v1.

Boudghene Stambouli O (2017) Réactions cutanées et aggravation de dermatoses après applications de produits traditionnels à base d’épine vinette (Berberis vulgaris), phytothérapie (khella–fucus vésiculeux graines de carotte) et l’huile essentielle d’argan. Rev Fr Allergol 57: 246–247.

Boumediou A, Addoun S (2017) Étude ethnobotanique sur l’usage des plantes toxiques, en médecine traditionnelle, dans la ville de Tlemcen (Algérie). Université Abou Bekr Belkaîd. Faculte de Medecine Dr. B. Benzerdjeb – Tlemcen, Algérie.

Bousta D, Boukhira S, Aafi A, Ghanmi M, El-Mansouri L (2014) Ethnopharmacological study of anti–diabetic medicinal plants used in the Middle-Atlas region of Morocco (Sefrou region). Int J Pharma Res Health Sci 2: 75–79.

Bouyahya A, Abrini J, Et-Touys A, Bakri Y, Dakka N (2017) Indigenous knowledge of the use of medicinal plants in the North-West of Morocco and their biological activities. Eur J Integr Med 13: 9–25.

Brneuton J (1996) Plantes toxiques: végétaux dangereux pour l’homme et les animaux. (1ère édition). Ed, Technique et Documentation Lavoisier. Paris, France.

Bukhari SI, Manzoor M, Dhar MK (2018) A comprehensive review of the pharmacological potential of Crocus sativus and its bioactive apocarotenoids. Biomed Pharmacother 98: 733–745.

Bunchorntavakul C, Reddy KR (2013) Review article: herbal and dietary supplement hepatotoxicity. Aliment Pharmacol Ther 37: 3–17.

Cabanillas M, Fernandez-Redondo V, Toribio J (2006) Allergic contact dermatitis to plants in a Spanish dermatology department: A 7-year review. Contact Derm 55: 84–91.

Cadena-González AL, Sørensen M, Theilade I (2013) Use and valuation of native and introduced medicinal plant species in Campo Hermoso and Zetaquira, Boyacá, Colombia. J Ethnobiol Ethnomed 9: 23.

Chahal KK, Kaur M, Bhardwaj U, Singla N, Kaur A (2017) A review on chemistry and biological activities of Laurus nobilis L. essential oil. J Pharmacogn Phytochem 6: 1153–1161.

Chan KW, Wong VT, Tang SCW (2020) COVID-19: An Update on the epidemiological, clinical, preventive and therapeutic evidence and guidelines of integrative Chinese-Western Medicine for the management of 2019 novel coronavirus disease. Am J Chin Med 48: 737–762.

Cheminat A, Stampf JL, Benezra C (1984) Allergic contact dermatitis to laurel (Laurus nobilis L.): Isolation and identification of haptens. Arch Dermatol Res 276: 178–181.

Choi EM, Hwang JK (2004) Antiinflammatory, analgesic and antioxidant activities of the fruit of Foeniculum vulgare. Fitoterapia 75: 557–565.

Collins S, Martins X, Mitchell A, Teshome A, Arnason JT (2006) Quantitative ethnobotany of two East Timorese cultures. Econ Bot 60: 347–361.

Craft JD, Setzer WN (2017) The volatile components of parsley, Petroselinum crispum (Mill.) Fuss. Am J Essent Oil Nat Prod 5: 27–32.

Cronquist A (1982) An integrated system of classification of flowering plants. New York, United States: Columbia University Press.

Daoudi A, Aarab L, Abdel-Sattar E (2013) Screening of immunomodulatory activity of total and protein extracts of some Moroccan medicinal plants. Toxicol Ind Health 29: 245–253.

Daoudi A, Bachiri L, Bammou M, Ibijbijen J, Nassiri L (2015) Étude ethnobotanique au Moyen Atlas Central. Eur Sci J 11: 226–242.

Daoudi A, Bammou M, Ibijbijen J, Nassiri L (2017) Antibacterial activity of aqueous extracts of Anacyclus pyrethrum (L) Link and Corrigiola telephiifolia Pourr. from the Middle Atlas Region-Morocco. Eur Sci J 13: 116–128.

Dehghani F, Heshmatpour A, Panjehshahin M, Talaei-Khozani T (2012) Toxic effects of water/alcoholic extract of Syzygium aromaticum on sperm quality, sex hormones and reproductive tissues in male mouse. Eur J Biol 71: 95–102.

Derraji A (2020) Covid-19 au Maroc: retour d’expérience d’un pharmacien d’officine. J Alger Pharm 3: 75–79.

Derraji S, Mahassin F, Rhalem N, Ouzzif Z (2014) Hépatotoxicité par Chenopodium ambrosioides à propos de 3 observations (colligées à l’hôpital militaire d’instruction Mohammed V, Rabat – Maroc). Toxicol Anal Clin 26: 176–180.

Dextreit R (1984) La cure végétale, Toutes les plantes pour se guérir, Vol 3, Editions de la Revue “Vivre en Harmonie”. Paris, France.

Dhama K, Khan S, Tiwari R, Sircar S, Bhat S, Malik YS, Singh KP, Chaicumpa W, Bonilla-Aldana DK, Rodriguez-Morales AJ (2020) Coronavirus Disease 2019–COVID-19. Clin Microbiol Rev 33(4): e00028-20.

Diao WR, Hu QP, Zhang H, Xu JG (2014) Chemical composition, antibacterial activity and mechanism of action of essential oil from seeds of fennel (Foeniculum vulgare Mill.). Food Control 35: 109–116.

Dossou-Yovo HO, Vodouhè FG, Sinsin B (2017) Ethnobotanical survey of mangrove plant species used as medicine from Ouidah to Grand-Popo Districts, Southern Benin. Am J Ethnomed 4(1): 8.

Duarte J, Torres AI, Zarzuelo A (2000) Cardiovascular effects of visnagin on rats. Planta Med 66: 35–39.

Durasnel P, Vanhuffel L, Blondé R, Lion F, Galas T, Mousset-Hovaere M, Balaÿ I, Viscardi G, Valyi L (2014) Intoxications graves lors de traitements traditionnels par les plantes à Mayotte. Bull Soc Pathol Exot 107: 306–311.

Durnev AD, Lapitskaya AS (2013) The genotoxicology of plant compounds. Russ J Genet Appl Res 3: 388–398.

El Atki Y, Aouam I, El Kamari F, Taroq A, Lyoussi B, Oumokhtar B, Abdellaoui A (2019a) Phytochemistry, antioxidant and antibacterial activities of two Moroccan Teucrium polium L. subspecies: Preventive approach against nosocomial infections. Arab J Chem 13(2): 3866–3874.

El Atki Y, Aouam I, El Kamari F, Taroq A, Zejli H, Taleb M, Abdellaoui A (2020) Antioxidant activities, total phenol an flavonoid contents of two Teucrium polium subspecies extracts. Mor J Chem 8: 446–455.

El Atki Y, Aouam I, Taroq A, Lyoussi B, Taleb M, Abdellaoui A (2019b) Total phenolic and flavonoid contents and antioxidant activities of extracts from Teucrium polium growing wild in Morocco. Mater Today: Proc 13: 777–783.

El-Saber Batiha G, Magdy Beshbishy A, Wasef L, Elewa YHA, Al-Sagan A, Abd El-Hack ME, Taha AE, Abd-Elhakim Y, Prasad Devkota H (2020) Chemical constituents and pharmacological activities of garlic (Allium sativum L.): A review. Nutrients 12: 872.

Esquivel-Ferriño PC, Favela-Hernández JMJ, Garza- González E, Waksman N, Ríos MY, Camacho-Corona MdR (2012) Antimycobacterial activity of constituents from Foeniculum vulgare var. dulce grown in Mexico Molecules 17: 8471–8482.

Ez Zoubi Y, Bousta D, Farah AA (2020) A phytopharmacological review of a Mediterranean plant: Lavandula stoechas L. Clin Phytosci 6: 9.

Fennane M, Ibn Tattou M (1998) Catalogue des plantes vasculaires rares, menacées ou endémiques du Maroc. Bocconea 8: 5–243.

Fennane M, Ibn Tattou M, El Oulaidi J (2014) Flore pratique du Maroc. Vol. 3, Travaux Institut Scientifique. Sér. Botanique N° 40. Rabat, Maroc.

Fennane M, Ibn Tattou M, Mathez J, Ouyahya A, El Oulaidi J (1999) Flore pratique du Maroc. Vol. 1, Travaux Institut Scientifique, Sér. Botanique N° 36, Rabat, Maroc.

Fennane M, Ibn Tattou M, Ouyahya A, El Oulaidi J (2007) Flore pratique du Maroc. Vol. 2, Travaux Institut Scientifique. Sér. Botanique N° 38, Rabat, Maroc.

Flesch F (2005) Intoxications d’origine végétale. EMC-Médecine 2: 532–546.

GabAllah M, Kandeil A, Mousa AEB, Ahmed Ali M (2020) Antiviral activity of water extracts of some medicinal and nutritive plants from the Apiaceae family. Novel Res Microbiol J 4: 725–735.

Gardiner P (1999) Chamomile (Matricaria recutita, Anthemis nobilis). The Longwood Herbal Task Force, pp. 1–21.

Gattefossé J (1952) L’Ammi visnaga et la khelline. Rev Int Bot Appl Agric Trop 353-354: 116–123.

Gavliakova S, Biringerova Z, Buday T, Brozmanova M, Calkovsky V, Poliacek I, Plevkova J (2013a) Antitussive effects of nasal thymol challenges in healthy volunteers. Respir Physiol Neurobiol 187: 104–107.

Gavliakova S, Dolak T, Licha H, Krizova S, Plevkova J (2013b) Cineole, thymol and camphor nasal challenges and their effect on nasal symptoms and cough in an animal model. Acta Medica Martiniana 13: 5–13.

Gerenutti M, Modesto L, Carrara VA, Magalhães SA, Paulo S (2014) Maternal exposure to aqueous extract of Mentha pulegium L. inducing toxicity to embryo development in rats. Afr J Pharm Pharmacol 8: 609–614.

Ghorbani A, Esmaeilizadeh M (2017) Pharmacological properties of Salvia officinalis and its components. J Tradit Complement Med 7: 433–440.

Gille L, Monzote L, Stamberg W, Staniek K (2010) Toxicity of ascaridole from Chenopodium ambrosioides in mammalian mitochondria. BMC Pharmacol 10(suppl. 1): A10.

Grange JM, Davey RW (1990) Detection of antituberculous activity in plant extracts. J Appl Bacteriol 68: 587–591.

H.C.P. (2013) Monographie de la Région Meknès_Tafilalt (Haut Commissariat au Plan, Direction Régionale de Meknès, Maroc.

H.C.P. (2018) Recensement Général de la Population et de l’Habitat au Maroc 2014. In Haut-commissariat au Plan. http://rgphentableaux.hcp.ma/Default1/ (accessed 10 March 2021).

Hadi MY, Hameed IH, Ibraheam IA (2017) Mentha pulegium: Medicinal uses, anti-hepatic, antibacterial, antioxidant effect and analysis of bioactive natural compounds: A review. Res J Pharm Technol 10: 1827–1831.

Hammiche V, Merad R, Azzouz M (2013) Plantes toxiques à usage médicinal du pourtour méditerranéen. Hammiche V, Merad R, Azzouz M, eds. France, Paris: Springer-Verlag, p. 393.

Haque A, Khatun R, Yaakob Z (2015) Gas chromatography mass spectrometry analysis and in vitro antibacterial activity of essential oil from Trigonella foenum-graecum. Asian Pac J Trop Biomed 5: 1033-1036.

Hardel DK, Laxmidhar S (2011) A review on phytochemical and pharmacological of Eucalyptus globulus: A multipurpose tree. Int J Ayurveda Res 2: 1527–1530.

Hashmi MA, Khan A, Hanif M, Farooq U, Perveen S (2015) Traditional uses, phytochemistry, and pharmacology of Olea europaea (olive). Evid Based Complement Alternat Med 2015: 541591.

He F, Deng Y, Li W (2020) Coronavirus disease 2019: What we know? J Med Virol 92: 719–725.

Hebi M, Eddouks M (2019) Hypolipidemic and antioxidant activities of Corrigiola telephiifolia in diabetic rats. Cardiovasc Hematol Agents Med Chem 17: 47–51.

Hebi M, Eddouks M (2020) Antidiabetic effect of aqueous Corrigiola telephiifolia in streptozotocin-induced diabetic rats. Nat Prod J 10: 61–68.

Hedayat KM, Lapraz JC, Schuff B (2020) The Theory of Endobiogeny. Vol. 4, Bedside Handbook, Academic Press.

Hussain W, Haleem KS, Khan I, Tauseef I, Qayyum S, Ahmed B, Riaz MN (2017) Medicinal plants: A repository of antiviral metabolites. Future Virol 12: 299–308.

Jain SK (1964) The role of botanist in folklore research. Folklore 5: 145–150.

Jamshidi-Kia F, Lorigooini Z, Asgari S, Saeidi K (2018) Iranian species of Verbascum: A review of botany, phytochemistry, and pharmacological effects. Toxin Rev 38(4): 255–262.

Jassim SAA, Naji MA (2003) Novel antiviral agents: A medicinal plant perspective. J Appl Microbiol 95: 412–427.

Kahouadji A (1986) Recherches floristiques sur le massif montagneux des Béni-Snassène (Maroc oriental). Thèse d’Université des Sciences et Techniques, Languedoc, Montpellier.

Karimi E, Oskoueian E, Karimi A, Noura R, Ebrahimi M (2017) Borago officinalis L. flower: A comprehensive study on bioactive compounds and its health-promoting properties. J Food Meas Charact 12: 826–838.

Kayani S, Ahmad M, Zafar M, Sultana S, Khan MPZ, Ashraf MA, Hussain J, Yaseen G (2014) Ethnobotanical uses of medicinal plants for respiratory disorders among the inhabitants of Gallies – Abbottabad, Northern Pakistan. J Ethnopharmacol 156: 47–60.

Keddad A, Baaliouamer A, Hazzit M (2016) Chemical composition and antioxidant activity of essential oils from umbels of Algerian Ammi visnaga (L.). J Essent Oil Bear Plants 19: 1243–1250.

Kharchoufa L, Alami Merrouni I, Yaman A, Elachouri M (2018) Profile on medicinal plants used by the people of North Eastern Morocco: Toxicity concerns. Toxicon 154: 90–113.

Khazaei M, Nematollahi-Mahani SN, Mokhtari T, Sheikhbahaei F (2018) Review on Teucrium polium biological activities and medical characteristics against different pathologic situations. J Contemp Med Sci 4(1): 1–6.

Kiran C, Prasad DN (2014) A review on: Nerium oleander Linn. (Kaner). Int J Pharmacogn Phytochem Res 6: 593–597.

Klauke A, Racz I, Pradier B, Markert A, Zimmer AM, Gertsch J, Zimmer A (2014) The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. Eur Neuropsychopharmacol 24: 608–620.

Klimek-Szczykutowicz M, Szopa A, Ekiert H (2020) Citrus limon (lemon) phenomenon—A review of the chemistry, pharmacological properties, applications in the modern pharmaceutical, food, and cosmetics industries, and biotechnological studies. Plants 9(1): 119.

Kompelly A, Kompelly S, Vasudha B, Narender B (2019) Rosmarinus officinalis L.: An update review of its phytochemistry and biological activity. J Drug Deliver Ther 9: 323–330.

Kooti W, Moradi M, Ali Akbari S, Sharafi-Ahvazi N, Asadi-Samani M, Ashtary-Larky D (2015) Therapeutic and pharmacological potential of Foeniculum vulgare Mill: A review. J HerbMed Pharmacol 4(1): 1–9.

Kubica P, Szopa A, Dominiak J, Luczkiewicz M, Ekiert H (2020) Verbena officinalis (common vervain) – A review on the investigations of this medicinally important plant species. Planta Med 86: 1241–1257.

Kumar Gupta S, Sharma A (2014) Medicinal properties of Zingiber officinale Roscoe-A review. J Pharm Biol Sci 9: 124–129.

Kumar R, Mishra AK, Dubey NK, Tripathi YB (2007) Evaluation of Chenopodium ambrosioides oil as a potential source of antifungal, antiaflatoxigenic and antioxidant activity. Int J Food Microbiol 115: 159–164.

Kunzemann J, Herrmann K (1977) Isolation and identification of flavon (ol)-O-glycosides in caraway (Carum carvi L.), fennel (Foeniculum vulgare Mill.), anise (Pimpinella anisum L.), and coriander (Coriandrum sativum L.), and of flavon-C-glycosides in anise. I. Phenolics of spices (author’s transl). Z Lebensm Unters Forsch 164: 194–200.

Lakmichi H, Bakhtaoui FZ, Gadhi CA, Ezoubeiri A, Jahiri El, Mansouri El, Zrara I, Loutfi K (2011) Toxicity profile of the aqueous ethanol root extract of Corrigiola telephiifolia Pourr. (Caryophyllaceae) in rodents. Evid Based Complement Alternat Med 2011: 317090.

Lamarti A, Badoc A, Carde JP (1993) Étude chromatographique de l’huile essentielle de la plantule de fenouil amer (Foeniculum vulgare Mill.); caractéristiques spectrales (uv, ir,sm) de ses constituants. Bull Soc Pharm 132: 73–89.

Levorato S, Dominici L, Fatigoni C, Zadra C, Pagiotti R, Moretti M, Villarini M (2018) In vitro toxicity evaluation of estragole-containing preparations derived from Foeniculum vulgare Mill. (fennel) on HepG2 cells. Food Chem Toxicol 111: 616–622.

Li XJ, Yang YJ, Li YS, Zhang WK, Tang HB (2016) Tang α-pinene, linalool, and 1-octanol contribute to the topical anti-inflammatory and analgesic activities of frankincense by inhibiting COX-2. J Ethnopharmacol 179: 22–26.

Lima CF, Carvalho F, Fernandes E, Bastos ML, Santos-Gomes P, Fernandes-Ferreira M, Pereira-Wilson C (2003) Evaluation of toxic/protective effects of the essential oil of Salvia officinalis on freshly isolated rat hepatocytes. Toxicol In Vitro 18: 457–465.

Lin J, Puckree T, Mvelase TP (2002) Anti-diarrhoeal evaluation of some medicinal plants used by Zulu traditional healers. J Ethnopharmacol 79: 53–56.

Lobstein A, Couic-Marinier F, Koziol N (2018) Huile essentielle d’Eucalyptus globulus. Actual Pharm 57: 59–61.

Lodhi S, Vadnere GP, Sharma VK, Usman M (2017) Marrubium vulgare L.: A review on phytochemical and pharmacological aspects. J Intercult Ethnopharmacol 6: 429–452.

Luo L, Jiang J, Wang C, Fitzgerald M, Hu W, Zhou Y, Zhang H, Chen S (2020) Analysis on herbal medicines utilized for treatment of COVID-19. Acta Pharm Sin B 10: 1192–1204.

Martin GJ (2014) Ethnobotany: A Methods Manual. Boston, MA: Springer, pp. 296.

Martins RDP, Roseli AS, Gomes ACG, Malpass MHO (2019) Chemical characterization of Lavandula dentata L. essential oils grown in Uberaba-MG. Cienc Rural 49(8): e20180964.

Mazokopakis E, Lazaridou S, Tzardi M, Mixaki J, Diamantis I, Ganotakis E (2004) Acute cholestatic hepatitis caused by Teucrium polium L. Phytomedicine 11: 83–84.

Milpied-Homsi B (2009) Progrès en dermato-allergologie. John Libbey Eurotext, Bordeaux.

Mimica‐Dukić N, Kujundžić S, Soković M, Couladis M (2003) Essential oil composition and antifungal activity of Foeniculum vulgare Mill. obtained by different distillation conditions. Phytother Res 17: 368–371.

Miraj S, Kiani S (2016a) A review study of therapeutic effects of Salvia officinalis L‏. Der Pharm Lett 8: 299–303.

Miraj S, Kiani S (2016b) Study of pharmacological effect of Mentha pulegium: A review. Der Pharm Lett 8: 242–245.

Mittal M, Gupta N, Parashar P, Mehra V, Khatri M (2014) Phytochemical evaluation and pharmacological activity of Syzygium aromaticum: A comprehensive review. Int J Pharm Pharm Sci 6: 67–72.

Mohamad RH, El-Bastawesy AM, Abdel-Monem MG, Noor AM, Al-Mehdar HA, Sharawy SM, El-Merzabani MM (2011) Antioxidant and anticarcinogenic effects of methanolic extract and volatile oil of fennel seeds (Foeniculum vulgare). J Med Food 14: 986–1001.

Mohamed A, El-Hamd H, El-Sayed MA, Hegazy ME, Helaly SE, Esmail AM, Mohamed NS (2010) Chemical constituents and biological activities of Artemisia herba-alba. Rec Nat Prod 4(1): 1–25.

Mohammadi Nejad S, Özgüneş H, Başaran N (2017) Pharmacological and toxicological properties of eugenol. Turk J Pharm Sci 14: 201–206.

Moufid A, Eddouks M (2012) Artemisia herba alba: A popular plant with potential medicinal properties. Pak J Biol Sci 15: 1152–1159.

Najem M, Bachiri L, Bouiamrine EH, Ibijbijen J, Nassiri L (2020c) Overview of some toxicplants for medicinal use: the case of the central Middle Atlas – Morocco. Ethnobot Res Appl 19: 1–39.

Najem M, Belaidi R, Harouak H, Bouiamrine EH, Ibijbijen J, Nassiri L (2018b) Occurrence de plantes toxiques en phytothérapie traditionnelle dans la région du Moyen Atlas central Maroc. J Anim Plant Sci 35: 5651–5673.

Najem M, Belaidi R, Slimani I, Bouiamrine EH, Ibijbijen J, Nassiri L (2018a) Pharmacopée traditionnelle de la région de Zerhoun – Maroc -: connaissances ancestrales et risques de toxicité. Int J Biol Chem Sci 12: 2797–2807.

Najem M, Daoudi A, Bouiamrine EH, Ibijbijen J, Nassiri L (2019b) Biodiversity of poisonous medicinal plants solicited in the traditional phytotherapy of the central Middle Atlas -Morocco. Ethnobot Res Appl 18: 1–23.

Najem M, Harouak H, Ibijbijen J, Nassiri L (2020a) Oral disorders and ethnobotanical treatments: A field study in the central Middle Atlas (Morocco). Heliyon 6(8): e04707.

Najem M, Ibijbijen J, Nassiri L (2019a) Quantitative ethnobotanical study of poisonous medicinal plants used in the traditional pharmacopoeia of the Central Middle Atlas Region: Morocco. Ethnobot Res Appl 18: 1–17.

Najem M, Ibijbijen J, Nassiri L (2020b) Vernacular names of toxic plants used as medicine in the central Middle Atlas – Morocco. Ethnobot Res Appl 20: 1–30.

Najem M, Ibijbijen J, Nassiri L (2021b) Ethnobotanical treatment of respiratory diseases in the central Middle Atlas (Morocco): Qualitative and quantitative approach. Eur J Integrat Med 46: 101358.

Najem M, Nassiri L, Ibijbijen J (2021a) Vernacular names of plants between diversity and potential risks of confusion: Case of toxic plants used in medication in the central Middle Atlas, Morocco. J Pharm Pharmacogn Res 9: 222–250.

Najem M, Nassiri L, Ibijbijen J 2021c) Origin of vernacular names of plants: Case of toxic plants for medicinal use in the central Middle Atlas – Morocco. Interdiscip Sci Rev. DOI: 10.1080/03080188.2021.1918371.

Nassiri L, Zarkani S, Daoudi A, Bammou M, Bouiamrine EH, Ibijbijen J (2016) Contribution à l’élaboration d’un catalogue ethnobotanique de la commune rurale d’Aguelmous (Province de Khénifra, Maroc). Int J Innov Appl Stud 17: 373–387.

Nawash O, Shudiefat M, Al-Tabini R, Al-Khalidi K (2013) Ethnobotanical study of medicinal plants commonly used by local Bedouins in the Badia region of Jordan. J Ethnopharmacol 148: 921–925.

Ni L, Zhou L, Zhou M, Zhao J, Wang DW (2020) Combination of western medicine and Chinese traditional patent medicine in treating a family case of COVID-19. Front Med 14: 210–214.

Nolkemper S, Reichling J, Stintzing FC, Carle R, Schnitzler P (2006) Antiviral effect of aqueous extracts from species of the Lamiaceae family against herpes simplex virus type 1 and type 2 in vitro. Planta Med 72: 1378–1382.

Olaiya CO, Soetan KO (2014) A review of the health benefits of fenugreek (Trigonella foenum-graecum L.): Nutritional, biochemical and pharmaceutical perspectives. Am J Soc Issues Humanit 4: 3–12.

Oliveira AP, Valentão P, Pereira JA, Silva BM, Tavares F, Andrade PB (2009) Ficus carica L.: Metabolic and biological screening. Food Chem Toxicol 47: 2841–2846.

Orav A, Raal A, Arak E (2008) Essential oil composition of Pimpinella anisum L. fruits from various European countries. Nat Prod Res 22: 227–232.

Ostad SN, Soodi M, Shariffzadeh M, Khorshidi N, Marzban H (2001) The effect of fennel essential oil on uterine contraction as a model for dysmenorrhea, pharmacology and toxicology study. J Ethnopharmacol 76: 299–304.

Ould El Hadj M, Didi M, Hadj-Mahammed M, Zabeirou H (2003) Place des plantes spontanées dans la médicine traditionnelle de la région d’Ouargla (Sahara septentrional Est). Courr Savoir 3: 47–51.

Pankaj S, Lokeshwar T, Mukesh B, Vishnu B (2011) Review on neem (Azadirachta indica): Thousand problems one solution. Int Res J Pharm 2: 97–102.

Parejo I, Viladomat F, Bastida J, Schmeda-Hirschmann G, Burillo J, Codina C (2004) Bioguided isolation and identification of the nonvolatile antioxidant compounds from fennel (Foeniculum vulgare Mill.) waste. J Agric Food Chem 52: 1890–1897.

Parthiban R, Vijayakumar S, Prabhu S, Yabesh JM (2016) Quantitative traditional knowledge of medicinal plants used to treat livestock diseases from Kudavasal taluk of Thiruvarur district, Tamil Nadu, India. Rev Bras Farmacogn 26: 109–121.

Patrakar R, Mansuriya M, Patil P (2012) Phytochemical and pharmacological review on Laurus nobilis. Int J Pharm Chem Sci 1: 595–602.

Peana AT, D’Aquila PS, Chessa ML, Moretti MDL, Serra G, Pippia P (2003) Pippia (-)-linalool produces antinociception in two experimental models of pain. Eur J Pharmacol 460: 37–41.

Pelkonen O, Abass K, Wiesner J (2013) Thujone and thujone-containing herbal medicinal and botanical products: Toxicological assessment. Regul Toxicol Pharmacol 65: 100–107.

Peng C, Zhu Z, Shi Y, Wang X, Mu K, Yang Y, Zhang X, Xu Z, Zhu W (2020) Exploring the binding mechanism and accessible angle of SARS-CoV-2 spike and ACE2 by molecular dynamics simulation and free energy calculation. ChemRxiv 11: 1–14.

Pereira OR, Macias RI, Domingues MR, Marin JJ, Cardoso SM (2019) Hepatoprotection of Mentha aquatica L., Lavandula dentata L. and Leonurus cardiaca L. Antioxidants 8(8): 267.

Pierre M, Lis M (1992) Au bonheur des plantes. Paris, France: Ed. Belford, pp. 476.

Prasanth Reddy V, Ravi Vital K, Varsha PV, Satyam S (2014) Review on Thymus vulgaris traditional uses and pharmacological properties. Med Aromat Plant 3: 3.

Rafieian-Kopaei M, Nasri H, Baradaran A (2014) Teucrium polium: Liver and kidney effects. J Res Med Sci 19: 478–479.

Ranasinghe P, Pigera S, Premakumara GS, Galappaththy P, Constantine GR, Katulanda P (2013) Medicinal properties of ‘true’ cinnamon (Cinnamomum zeylanicum): A systematic review. BMC Complement Alternat Med 13: 275.

Reyes-Becerril M, Angulo C, Sanchez V, Vázquez-Martínez J, López MG (2019) Antioxidant, intestinal immune status and anti-inflammatory potential of Chenopodium ambrosioides L. in fish: In vitro and in vivo studies. Fish Shellfish Immunol 86: 420–428.

Rodríguez-Morales AJ, MacGregor K, Kanagarajah S, Patel D, Schlagenhauf P (2020) Going global – Travel and the 2019 novelcoronavirus. Travel Med Infect Dis 33: 101578.

Santos FA, Rao VSN (2000) Antiinflammatory and antinociceptive effects of 1,8-cineole a terpenoid oxide present in many plant essential oils. Phytother Res 14: 240–244.

Savo V, Giulia C, Maria GP, David R (2011) Folk phytotherapy of the Amalfi Coast (Campania, Southern Italy). J Ethnopharmacol 135: 376–392.

Semyaril H, Owlia P, Farhadi S, Saeed TM (2011) Evaluation of antimicrobial effect of Ammi visnaga against oral streptococci. J Microbiol Antimicrob 3: 126–129.

Shankar A, Dubey A, Saini D, Prasad CP (2020) Role of complementary and alternative medicine in prevention and treatment of COVID-19: An overhyped hope. Chin J Integr Med 26: 565–567.

Sharma AD, Kaur I (2020) Molecular docking studies on jensenone from eucalyptus essential oil as a potential inhibitor of COVID 19 corona virus infection. Res Rev Biotechnol Biosci 7: 59–66.

Shaza MA (2016) Phytochemical screening of Petroselinum crispum (Mill.) Fuss and in vitro evaluation of its antimicrobial activity against some uropathogens. Arab J Med Aromat Plant 2: 86–98.

Sijelmassi A (1993) Les plantes médicinales du Maroc. Casablanca, Maroc: Edition Le Fennec.

Singh N, Rao AS, Nandal A, Kumar S, Yadav SS, Ganaie SA, Narasimhan B (2021) Phytochemical and pharmacological review of Cinnamomum verum J. Presl-a versatile spice used in food and nutrition. Food Chem 338: 127773.

Singhal T (2020) A review of coronavirus disease-2019 (COVID-19). Indian J Pediatr 87: 281–286.

Tahri N, El Basti A, Zidane L, Rochdi A, Douira A (2012) Etude ethnobotanique des plantes medicinales dans la province de Settat (Maroc). J For Fac 12: 192–208.

Talaat IM, Khattab HI, Ahmed AM (2013) Changes in growth, hormones levels and essential oil content of Ammi visnaga L. plants treated with some bio-regulators. Saudi J Biol Sci 21: 355–365.

Tas A, Ozbek H, Atasoy N, Altug ME, Ceylan E (2006) Evaluation of analgesic and anti-inflammatory activity of Pimpinella anisum fixed oil extract. Indian Vet J 83: 840–843.

Tatli I, Akdemir ZS (2004) Chemical constituents of Verbascum L. species. Fabad J Pharm Sci 29: 93–107.

Teixeira B, Marques A, Ramos C, Batista I, Serrano C, Matos O, Neng NR, Nogueira JMF, Saraiva JA, Nunes ML (2012) European pennyroyal (Mentha pulegium) from Portugal: Chemical composition of essential oil and antioxidant and antimicrobial properties of extracts and essential oil. Ind Crops Prod 36: 81–87.

Tirapelli CR, de Andrade CR, Cassano AO, De Souza FA, Ambrosio SR, da Costa FB, de Oliveira AM (2007) Antispasmodic and relaxant effects of the hidroalcoholic extract of Pimpinella anisum (Apiaceae) on rat anococcygeus smooth muscle. J Ethnopharmacol 110: 23–29.

Vanachayangkul P, Byer K, Khan S, Butterweck V (2010) An aqueous extract of Ammi visnaga fruits and its constituents khellin and visnagin prevent cell damage caused by oxalate in renal epithelial cells. Phytomedicine 17: 653–658.

Vitalini S, Iriti M, Puricelli C, Ciuchi D, Segale A, Fico G (2013) Traditional knowledge on medicinal and food plants used in Val San Giacomo (Sondrio, Italy)—An alpine ethnobotanical study. J Ethnopharmacol 145: 517–529.

Wang L, Zhang T, Zhang JL, Yu Y, Gan ZM (2012) Experimental study of Chinese herb Foeniculum vulgare Mill on liver hepatic fibrosis and potassium supplement in rats. J Xinjiang Med Univ 9: 1–9.

Zaghlol DA, Kamel E, Mohammed D, Abbas NH (2012) The possible toxic effect of different doses of Nigella sativa oil on the histological structure of the liver and renal cortex of adult male albino rats. Egypt J Histol 35: 127–136.

Zakariya I, Elhamdaoui O, Ibn Lahmar Andaloussi Z, Chergui A, Taghzouti K, Nejjari R (2020) Acute diuretic activity of the aqueous ethanol root extract of Corrigiola telephiifolia Pourr. in rats. Pharmacogn J 12: 1552-1558.

Zaman W, Saqib S, Ullah F, Ayaz A, Ye J (2020) COVID-19: Phylogenetic approaches may help in finding resources for natural cure. Phytother Res 34: 2783–2785.

Zaoui A, Cherrah Y, Mahassini N, Alaoui K, Amarouch H, Hassar M (2002) Acute and chronic toxicity of Nigella sativa fixed oil. Phytomedicine 9: 69–74.

Zeggwagh AA, Lahlou Y, Bousliman Y, Ousliman Y (2013) Enquete sur les aspects toxicologiques de la phytotherapie utilisee par un herboriste à Fes, Maroc. Pan Afr Med J 14: 125.

Zenjari L, Elfatoiki FZ, Hali F, Chiheb S (2019) Phytophotodermatose des mains à Marrubium vulgare chez une enfant. Ann Dermatol Venereol 146: A193–A194.

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Moroccan medicinal plants against COVID-19

Pharmaceutical Science, , , , ,


J Pharm Pharmacogn Res 10(2): 227-238, 2022.

DOI: https://doi.org/10.56499/jppres21.1200_10.2.227

Original Article

Molecular docking study of the main phytochemicals of some medicinal plants used against COVID-19 by the rural population of Al-Haouz region, Morocco

[Estudio de acoplamiento molecular de los principales fitoquímicos de algunas plantas medicinales utilizadas contra el COVID-19 por la población rural de la región de Al-Haouz, Marruecos]

Ridwane Ghanimi1*, Ahmed Ouhammou2, Yassine El Atki3, Mohamed Cherkaoui1

1Laboratory of Pharmacology, Neurobiology, Anthropobiology, Environment and Behaviour, Department of Biology, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakech, BP 2390, 40000, Morocco.

2Laboratory of Microbial Biotechnologies, Agrosciences and Environment (BioMAgE), Agrosciences, Phytobiodiversity and Environment Team, Regional Herbarium ‘MARK’, Department of Biology, Faculty of Sciences Semlalia , Cadi Ayyad University, PO. Box 2390, Marrakech, 400001, Morocco.

3Laboratory of Physiology Pharmacology and Environmental Health, Department of Biology, Faculty of Sciences Dhar Mehraz,Sidi Mohamed Ben Abdellah University, Fez, Morocco.

*E-mail: ghanimiridwane@gmail.com, ridwane.ghanimi@ced.uca.ma

Abstract

Context: The infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global health emergency. The management of this crisis requires the discovery of new drugs able to cure or reduce the severity of SARS-CoV-2.

Aims: To explore the medicinal plants consumed by the rural population of Al-Haouz region against the emergence of the COVID-19, and to assess in silico the main phytochemicals present in the essential oils and the extracts of these medicinal plants, as potential inhibitors of the COVID-19 main protease (Mpro).

Methods: The survey was conducted through a semi-structured questionnaire among 85 respondents aged 30 years and above, in the Al-Haouz region, Morocco. AutoDock Vina, was used to assess the binding affinity of the phytochemicals to the Mpro.

Results: Eleven wild medicinal species were cited; 10 belonging to the Lamiaceae family and one to the Compositae family. Thymus saturejoides Coss., Artemisia herba-alba Asso.and Mentha suaveolens Ehrh. were respectively the three most cited species during the survey. The rosmarinic acid (-7.7 kcal/mol), hesperetin (-7.2 kcal/mol), gallocatechin (-7.2 kcal/mol) and cyasterone (-7.2 kcal/mol) have shown the higher inhibitory potential against covid-19 Mpro respectively.

Conclusions: In addition to their different recognized biological activities, the medicinal plants used in the Al-Haouz region have shown good inhibitory potential against SARAS-CoV-2 Mpro. Furthermore, the phytochemicals that exhibited the highest inhibitory potentials in this virtual study require further investigation in vitro and in vivo.

Keywords: COVID-19; ethnomedicine; medicinal plants; molecular docking; Morocco; SARS-CoV-2.

Resumen

Contexto: La infección por el coronavirus 2 del síndrome respiratorio agudo severo (SARS-CoV-2) es una emergencia sanitaria mundial. El manejo de esta crisis requiere el descubrimiento de nuevos medicamentos capaces de curar o reducir la gravedad del SARS-CoV-2.

Objetivos: Explorar las plantas medicinales consumidas por la población rural de la región de Al-Haouz frente a la aparición del COVID-19, y evaluar in silico los principales fitoquímicos presentes en los aceites esenciales y los extractos de estas plantas medicinales, como potenciales inhibidores. de la proteasa principal COVID-19 (Mpro).

Métodos: La encuesta se realizó a través de un cuestionario semiestructurado entre 85 encuestados de 30 años o más, en la región de Al-haouz, Marruecos. Se utilizó AutoDock Vina para evaluar la afinidad de unión de los fitoquímicos al Mpro.

Resultados: Se citaron once especies medicinales silvestres; 10 pertenecientes a la familia Lamiaceae y una a la familia Compositae. Thymus saturejoides Coss., Artemisia herba-alba Asso. y Mentha suaveolens Ehrh. fueron, respectivamente, las tres especies más citadas durante la encuesta. El ácido rosmarínico (-7,7 kcal/mol), la hesperetina (-7,2 kcal/mol), la galocatequina (-7,2 kcal/mol) y la ciasterona (-7,2 kcal/mol) han mostrado el mayor potencial inhibitorio frente al covid-19 Mpro, respectivamente.

Conclusiones: Además de sus diferentes actividades biológicas reconocidas, las plantas medicinales utilizadas en la región de Al-Haouz han mostrado un buen potencial inhibitorio contra SARAS-CoV-2 Mpro. Además, los fitoquímicos que exhibieron los potenciales inhibidores más altos en este estudio virtual requieren más investigación in vitro e in vivo.

Palabras Clave: acoplamiento molecular; COVID-19; etnomedicina; Marruecos; plantas medicinales; SARS-CoV-2.

This image has an empty alt attribute; its file name is jppres_pdf_free.png

Download the PDF file .

 
Citation Format: Ghanimi R, Ouhammou A, El Atki Y, Cherkaoui M (2022) Molecular docking study of the main phytochemicals of some medicinal plants used against COVID-19 by the rural population of Al-Haouz region, Morocco. J Pharm Pharmacogn Res 10(2): 227–238. https://doi.org/10.56499/jppres21.1200_10.2.227

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)