Tag Archives: SARS-CoV-2

In-silico study of volatile compounds and COVID-19

J. Pharm. Pharmacogn. Res., vol. 10, no. 3, pp. 469-485, May-June 2022.

Original Article

Volatile compounds from Phyla scaberrima (Juss. ex Pers.) Moldenke and Dysphania ambrosioides (L.) Mosyakin & Clemants as possible SARS-CoV-2 protease inhibitors: Identification and in-silico study

[Compuestos volátiles de Phyla scaberrima (Juss. ex Pers.) Moldenke y Dysphania ambrosioides (L.) Mosyakin & Clemants como posibles inhibidores de proteasas de SARS-CoV-2: Identificación y estudio in-silico]

Neyder Contreras-Puentes1*, Manuel Salas-Moreno2,3, Lina Mosquera-Chaverra2, Leonomir Córdoba-Tovar4, Antistio Alviz-Amador5

1GINUMED, Medicine, Corporation University Rafael Nuñez, Cartagena D.T y C, Colombia.

2Faculty of Naturals Sciences, Biology Department, Biosistematic Research Group, Technological University of Chocó, Quibdó, Colombia.

3Analytical Chemistry and Biomedicine Group. Exacts and Natural Sciences Faculty. University of Cartagena. Cartagena, Colombia.

4Research Group Natural Resources and Environmental Toxicology, Technological University of Chocó, Quibdó, Colombia.

 5Pharmacology and Therapeutics Group, University of Cartagena, Cartagena D.T y C., Colombia.

*E-mail: neyder.contreras@curnvirtual.edu.co

Abstract

Context: COVID-19 is a pandemic that has affected the entire population, characterized by multisystemic involvement. With around 130 million cases of infection and more than 2.5 million deaths globally. However, the development of a low-efficacy treatment has led to the study of natural products as possible therapeutic alternatives against SARS-CoV-2.

Aims: To identify volatile compounds present in two plants in the Colombian Pacific and carry out in-silico studies to search for promising inhibitory molecules against SARS-CoV-2 proteases.

Methods: This research carried out the identification of metabolites of two plants identified in the Colombian Pacific, called P. scaberrima (Juss. ex Pers.) Moldenke y D. ambrosioides (L.) Mosyakin & Clemants. Ethanolic extracts were obtained by rotary-evaporation and determinated by GC-MS. Subsequently, in-silico studies were carried out by molecular docking against Mpro and PLpro using Autodock-vina 1.1. Also, a prediction of ADMET properties using SwissADME and GUSAR-Online server was performed.

Results: Thus, 15 volatile compounds with similarities greater than 85% were identified from both extracts, mostly sesquiterpenic and monoterpenic compounds. The compounds that showed the highest affinity against Mpro were α-amorphene and phytol for PLpro. Likewise, these were contrasted with co-crystallized molecules such as boceprevir and VIR2-251 as control structures. Finally, the predictions of ADMET properties showed values consistent with the literature.

Conclusions: Therefore, the follow-up of in-silico studies with these plants from Colombian pacific are considered as possible tools in the search for active molecules against proteases linked to virus.

Keywords: Dysphania ambrosioides; GC-MS/MS; molecular docking; Phyla scaberrima; SARS-CoV-2.

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Resumen

Contexto: COVID-19 es una pandemia que ha afectado a toda la población mundial, caracterizada por compromisos multisistémicos. Con alrededor de 130 millones de casos de infección y más de 2,5 millones de muertes en todo el mundo. Sin embargo, el desarrollo de un tratamiento de baja eficacia ha llevado al estudio de productos naturales como posibles alternativas terapéuticas frente al SARS-CoV-2.

Objetivos: Identificar compuestos volátiles presentes en dos plantas del Pacifico colombiano y realizar estudios in-silico para la búsqueda de promisorias moléculas inhibidoras contra proteasas de SARS-CoV-2.

Métodos: En esta investigación se realizó la identificación de metabolitos de dos plantas identificadas en el Pacífico colombiano, llamadas P. scaberrima (Juss. ex Pers.) Moldenke y D. ambrosioides (L.) Mosyakin & ClemantsSe obtuvieron extractos etanólicos, preconcentrados con evaporación rotatoria y se determinaron por GC-MS. Posteriormente, se realizaron estudios in-silico mediante acoplamiento molecular contra Mpro y PLpro utilizando Autodock-vina. Además, prediciendo las propiedades de ADMET mediante SwissADME y GUSAR-Online.

Resultados: Se identificaron 15 compuestos volátiles con similitudes superiores al 85% de ambos extractos, en su mayoría compuestos sesquiterpénicos y monoterpénicos. Los compuestos que mostraron la mayor afinidad contra Mpro fue α-amorfeno y fitol para PLpro. Asimismo, se contrastaron con moléculas co-cristalizadas como boceprevir y VIR2-251 como estructuras control. Finalmente, en las predicciones de propiedades ADMET mostraron valores consistentes con la literatura.

Conclusiones: Se consideró el seguimiento de estudios in-silico con estas plantas del Pacífico colombiano como posibles herramientas en la búsqueda de moléculas activas frente a proteasas ligadas al virus.

Palabras Clave: acoplamiento molecular; Dysphania ambrosioides; GC-MS/MS; Phyla scaberrima; SARS-CoV-2.

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Citation Format: Contreras-Puentes N, Salas-Moreno MH, Mosquera-Chaverra L, Córdoba-Tovar L, Alvíz-Amador AA (2022) Volatile compounds from Phyla scaberrima (Juss. ex Pers.) Moldenke y Dysphania ambrosioides (L.) Mosyakin & Clemants as possible SARS-CoV-2 protease inhibitors: Identification and in-silico study. J Pharm Pharmacogn Res 10(3): 469–485.
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

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

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

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.

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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.
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

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

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

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
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.
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Roselle flower for immunomodulatory adjuvant therapy in COVID-19

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

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
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.
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Moroccan medicinal plants against COVID-19



J Pharm Pharmacogn Res 10(2): 227-238, 2022.

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
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.

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Volume 9, Suppl. 1 (MICPS 2021)

J Pharm Pharmacogn Res 9(Suppl. 1), (October) 2021

1st Makassar International Conference on Pharmaceutical Sciences

(MICPS 2021)

Empowering Natural Product in Drugs Discovery and Development

Faculty of Pharmacy Universitas Muslim Indonesia

Makassar, Indonesia

September 25-26, 2021

Conference Proceedings  [1.3 Mb]
Editing, design and realization: Gabino Garrido, Marisela Valdés, Xavier Garrido, Muammar Fawwaz, Aktsar Roskiana Ahmad
Editorial Scientific Council: Muammar Fawwaz, Aktsar Roskiana Ahmad, A. Emelda, Nurmaya Effendi

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

B-cell epitope of SARS-CoV-2 and COVID-19 vaccine candidate



J Pharm Pharmacogn Res 9(6): 766-779, 2021.

Original article

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

[Investigación viroinformática de la región conservada del epítopo de células B en el linaje SARS-CoV-2 B.1.1.7 aislamientos originados en Indonesia para desarrollar una vacuna candidata contra COVID-19]

Arif N. M. Ansori1,2#, Reviany V. Nidom1,3*#, Muhammad K. J. Kusala1,2, Setyarina Indrasari1,3, Irine Normalina1,4, Astria N. Nidom1,3, Balqis Afifah1,3, Kartika B. Sari1,5, Nor L. Ramadhaniyah1,5, Mohammad Y. Alamudi1,3, Umi Cahyaningsih6, Kuncoro P. Santoso1,2, Heri Kuswanto5, Chairul A. Nidom1,2,3*

1Coronavirus and Vaccine Formulation Research Group, Professor Nidom Foundation, Surabaya, Indonesia.

2Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Riset AIRC Indonesia, Surabaya, Indonesia.

4Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

5Faculty of Science and Data Analytics, Institut Teknologi Sepuluh Nopember, Surabaya, Indonesia.

6Faculty of Veterinary Medicine, IPB University, Bogor, Indonesia.

#Both authors contributed equally.

*E-mail: reviany@pnfinstitute.org, nidomca@pnfinstitute.org, nidomca@fkh.unair.ac.id

Abstract

Context: SARS-CoV-2, a member of family Coronaviridae and the causative agent of COVID-19, is a virus which is transmitted to human and other mammals.

Aims: To analyze the B-cell epitope conserved region and viroinformatics-based study of the SARS-CoV-2 lineage from Indonesian B.1.1.7 isolates to invent a vaccine nominee for overcoming COVID-19.

Methods: The sequences of seven Indonesian B.1.1.7 isolates, Wuhan-Hu-1 isolate, and WIV04 isolate were extracted from the GISAID EpiCoV and GenBank, NCBI. MEGA X was employed to understand the transformations of amino acid in the S protein and to develop a molecular phylogenetic tree. The IEDB was implemented to reveal the linear B-cell epitopes. In addition, PEP-FOLD3 web server was utilized to perform peptide modeling, while docking was performed using PatchDock, FireDock, and the PyMOL software. Moreover, in silico cloning was developed by using SnapGene v.3.2.1 software.

Results: In this study, the changes of amino acid in all seven Indonesian B.1.1.7 isolates were uncovered. Furthermore, various peptides based on the B-cell epitope prediction, allergenicity prediction, toxicity prediction from S protein to generate a vaccine contrary to SARS-CoV-2 were identified. Furthermore, the development of in silico cloning using pET plasmid was successfully achieved.

Conclusions: This study exhibits the transformations of amino acid in Indonesian B.1.1.7 isolates, and proposes four peptides (“LTPGDSSSGWTAG”, “VRQIAPGQTGKIAD”, “ILPDPSKPSKRS”, and “KNHTSPDVDLG”) from S protein as the candidate for a peptide-based vaccine. However, further advance trials such as in vitro and in vivo testing are involved for validation.

Keywords: COVID-19; SARS-CoV-2; vaccine design; viroinformatics.

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Resumen

Contexto: SARS-CoV-2, un miembro de la familia Coronaviridae y el agente causante de COVID-19, es un virus que se transmite a humanos y otros mamíferos.

Objetivos: Analizar la región conservada del epítopo de células B y el estudio basado en viroinformática del linaje SARS-CoV-2 de los aislados B.1.1.7 de Indonesia para inventar una vacuna candidata para superar COVID-19.

Métodos: Las secuencias de siete aislamientos B.1.1.7 indonesios, el aislado Wuhan-Hu-1 y el aislado WIV04 se extrajeron de GISAID EpiCoV y GenBank, NCBI. Se empleó MEGA X para comprender las transformaciones de aminoácidos en la proteína S y para desarrollar un árbol filogenético molecular. El IEDB se implementó para revelar los epítopos de células B lineales. Además, se utilizó el servidor web PEP-FOLD3 para realizar el modelado de péptidos, mientras que el acoplamiento se realizó mediante PatchDock, FireDock y el software PyMOL. Además, la clonación in silico se desarrolló utilizando el software SnapGene v.3.2.1.

Resultados: En este estudio, se descubrieron los cambios de aminoácidos en los siete aislamientos de B.1.1.7 de Indonesia. Además, se identificaron varios péptidos basados en la predicción del epítopo de células B, la predicción de la alergenicidad, la predicción de la toxicidad de la proteína S para generar una vacuna contraria al SARS-CoV-2. Además, se logró con éxito el desarrollo de la clonación in silico utilizando el plásmido pET.

Conclusiones: Este estudio exhibe las transformaciones de aminoácidos en aislados B.1.1.7 de Indonesiay propone cuatro péptidos (“LTPGDSSSGWTAG”, “VRQIAPGQTGKIAD”, “ILPDPSKPSKRS” y “KNHTSPDVDLG”) de la proteína S como candidato para una vacuna basada en péptidos. Sin embargo, para la validación se requieren más ensayos in vitro e in vivo.

Palabras Clave: COVID-19; SARS-CoV-2; vaccine design; viroinformatics.

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Citation Format: Ansori ANM, Nidom RV, Kusala MKJ, Indrasari S, Normalina I, Nidom AN, Afifah B, Sari KB, Ramadhaniyah NL, Alamudi MY, Cahyaningsih U, Santoso KP, Kuswanto H, 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(6): 766–779.

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Methylene blue therapy against COVID-19



J Pharm Pharmacogn Res 9(3): 379-396, 2021.

Review

The rationale for methylene blue utility against SARS-CoV-2 infection complications

[Fundamentación de la utilidad del azul de metileno contra las complicaciones de la infección por SARS-CoV-2]

Gilberto L. Pardo Andreu

Center for Research and Biological Evaluations, Institute of Pharmaceutical and Food Sciences, University of Havana (UH), Av. 23 # 2317 b/ 214 and 222, La Coronela, La Lisa, PO 13600 Havana, Cuba.

*E-mail: gpardo@ifal.uh.cu

Abstract

Context: Almost one year after the onset of COVID-19 pandemic in Wuhan, China and still no specific therapy has emerged, counting millions of dead worldwide. The association of an uncontrolled SARS-CoV-2 replication and host-dependent mechanisms in COVID-19 pathogenesis suggest that any therapeutic strategy must combine antiviral drugs and adjuvant therapy to modulate the host’s responses. Owing to the multiplicity of mechanisms involved in COVID-19 pathogenic expressions, such as severe hypoxia, excessive inflammatory reaction and impaired immune response, an emerging therapeutic paradigm is the searching for agents acting as multifunctional drugs. Methylene blue (MB), the antique medication, seems to meet the above criterion.

Aims: To summarize the probable beneficial effects of MB against COVID-19 supported by a discussion of the drug mechanisms of action counteracting the pathogenic mechanisms of the disease.

Methods: PubMed, Google Scholar, and Scopus databases were used to collect the biomedical research on MB, and the discussed dataset finally included 150 published articles. Those COVID-19 pathogenic pathways possibly targeted by MB were critically appraised.

Results: It was found that MB may act as multimodal agent by targeting simultaneously several pathogenic mechanisms of COVID-19 as hypoxic damage, hyper-inflammatory reaction and death signaling activation. It also may act as a virucidal agent by preventing virus-induced metabolic re-orientation. Its high safety profile, low cost, along with the mechanisms discussed herein might be essential criteria to test MB as an adjuvant therapy against COVID-19.

Conclusions: Overall, this critical review provides theoretical grounds for MB clinical evaluation in the therapeutic management of SARS-CoV-2 infection.

Keywords: COVID-19; methylene blue; SARS-CoV-2.

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Resumen

Contexto: Casi un año después del inicio de la pandemia de COVID-19 en Wuhan, China, y aún no ha surgido una terapia específica, contando millones de muertos en todo el mundo. La asociación de una replicación no controlada del SARS-CoV-2 y los mecanismos dependientes del hospedero en la patogénesis del COVID-19 sugieren que cualquier estrategia terapéutica debe combinar fármacos antivirales y terapia adyuvante para modular las respuestas del hospedero. Debido a la multiplicidad de mecanismos involucrados en las expresiones patogénicas de la COVID-19, como la hipoxia severa, la reacción inflamatoria excesiva y la respuesta inmune deteriorada, un paradigma terapéutico emergente es la búsqueda de agentes que actúen como fármacos multifuncionales. El azul de metileno (AM), un antiguo medicamento, parece cumplir con el criterio anterior.

Objetivos: Resumir los probables efectos beneficiosos del AM contra la COVID-19 apoyados por una discusión de los mecanismos de acción del fármaco que pudieran contrarrestar los mecanismos patogénicos de la enfermedad.

Métodos: Se utilizaron las bases de datos PubMed, Google Scholar y Scopus para recopilar las investigaciones biomédicas sobre el AM, y el conjunto de datos que se discutió finalmente incluyó 150 artículos publicados. Se evaluaron críticamente aquellos mecanismos patogénicos de la COVID-19 posibles blancos farmacológicos del AM.

Resultados: Se encontró que el AM puede actuar como un agente multimodal al actuar simultáneamente sobre varios mecanismos patogénicos de la COVID-19 como el daño hipóxico, la reacción hiperinflamatoria y la activación de señalizaciones de muerte. También puede actuar como agente virucida al prevenir la reorientación metabólica del hospedero inducida por el virus. Su elevado perfil de seguridad, bajo costo, junto con los mecanismos discutidos en este documento, podrían ser criterios esenciales para probar el AM como terapia adyuvante contra la COVID-19.

Conclusiones En general, esta revisión crítica proporciona las bases teóricas para la evaluación clínica del AM en el manejo terapéutico de la infección por SARS-CoV-2.

Palabras Clave: azul de metileno; COVID-19; SARS-CoV-2.

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Citation Format: Pardo Andreu GL (2021) The rationale for methylene blue utility against SARS-CoV-2 infection complications. J Pharm Pharmacogn Res 9(3): 379–396.

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Ozone in COVID-19


J Pharm Pharmacogn Res 9(2): 126-142, 2021.

Original Article

Complementary application of the ozonized saline solution in mild and severe patients with pneumonia COVID-19: A non-randomized pilot study

[Aplicación de la solución salina ozonizada como terapia complementaria en pacientes COVID-19 con neumonía de estadía mediana a severa: Estudio piloto no aleatorizado]

Adriana Schwartz1,Gregorio Martínez-Sánchez2*, Alejandra M. de Lucía3, Sergio M. Viana4, Alina M. Constanta5

1Fiorella Clinic, Pain Management Unit, Madrid (28035), Spain.

2Scientific advisor, Freelance, Ancona (60126), Italy.

3Integrative Medicine Clinic, Madrid (28002), Spain.

4Cardio Care of Hospital High Care Marbella and Hospital CHIP of Malaga (29010), Spain.

5Hospital Virgen De La Paloma, Madrid (28003) Spain.

*E-mail: gregorcuba@yahoo.it

Abstract

Context: Currently, there is no effective antiviral therapy recommended for novel coronavirus pneumonia 2019 (COVID-19).

Aims: To assess the safety of ozonized saline solution (O3SS) used as a complementary therapy in adult COVID-19 patients.

Methods: Twenty-five adult patients hospitalized with mild to severe symptoms of COVID-19, who met the inclusion criteria and were treated from April 18 to April 26, 2020, at Virgen De La Paloma Hospital, Madrid, Spain were included in this study. Patients were assigned to receive standard care consisting ceftriaxone (250 mg – 2 g twice daily for 7 days) plus azithromycin (500 mg once daily for 5 days), of 200 – 400 mg hydroxychloroquine twice daily for 5-7 days plus tocilizumab 400 mg twice daily for 5 days, low molecular weight heparin and 40 to 60 mg metil-prednisone plus O3SS, 200 mL, 3-5 µg/mL per day for 10 days. No control group was included, the data was compared to clinical trials in this subject. Secondary endpoints assessed included the clinical status of participants, laboratory examinations, and duration of viral shedding.

Results: Patients with COVID-19 with mild to severe symptoms who received intravenous O3SS as an adjunct treatment experienced no side effects. The main results of O3SS treatment were a tendency to improve clinical symptoms without side effects. None of the patients treated died.

Conclusions: Early evidence of efficacy shown improvements in symptoms such as dyspnea, weakness, and reduction in body temperature were observed and corresponded to improvements in laboratory results including D-dimer, fibrinogen, lactate dehydrogenase, and C-reactive protein. These preliminary data will serve as the basis for a future study of the effectiveness of this therapy.

Keywords: COVID-19; ozone therapy; ozonized saline solution; pneumonia; SARS-CoV-2.

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Resumen

Contexto: Actualmente, no existe una terapia antiviral eficaz recomendada para la neumonía por el nuevo coronavirus 2019 (COVID-19).

Objetivos: Evaluar la seguridad de la solución salina ozonizada (O3SS) como terapia complementaria en pacientes adultos con COVID-19.

Métodos: Se incluyeron veinticinco pacientes adultos con síntomas leves a severos de COVID-19, que cumplieron con los criterios de inclusión. Estos fueron tratados del 18 al 26 de abril de 2020, en el Hospital Virgen de La Paloma, Madrid, España. Los pacientes fueron asignados para recibir atención estándar [ceftriaxona (250 mg – 2 g cada 12 h por 7 días); azitromicina (500 mg cada 24 h por 5 días); 200-400 mg de hidroxicloroquina cada 12 h por 5-7 días; tocilizumab 400 mg cada 12 h por 5 días; heparina y 40 a 60 mg de metil-prednisona] más O3SS, 200 mL, 3-5 µg/mL por día durante 10 días. No se incluyó ningún grupo de control, los datos se compararon con ensayos clínicos similares. Los criterios de valoración secundarios incluyeron el estado clínico de los participantes, los exámenes de laboratorio y la duración de la diseminación viral.

Resultados: Los pacientes con COVID-19 tratados que recibieron O3SS intravenoso como tratamiento complementario no experimentaron efectos secundarios. El tratamiento con O3SS tendió a mejorar los síntomas clínicos. Ninguno de los pacientes tratados falleció.

Conclusiones: Se observaron evidencias tempranas de mejoras en síntomas como disnea, debilidad y reducción de la temperatura corporal, que correspondieron con una mejora de variables como: el dímero D, fibrinógeno, lactato deshidrogenasa y proteína C reactiva. Estos datos preliminares servirán de base para un futuro estudio de la eficacia de esta terapia.

Palabras Clave: Clave: COVID-19; ozonoterapia; solución salina ozonizada, neumonía; SARS-CoV-2.

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Citation Format: Schwartz A, Martínez-Sánchez G, de Lucía AM, Viana SM, Constanta AM (2021) Complementary application of the ozonized saline solution in mild and severe patients with pneumonia COVID-19: A non-randomized pilot study. J Pharm Pharmacogn Res 9(2): 126–142.

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)