Tag Archives: COVID-19

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)

Phytotherapy against COVID-19 and risks of intoxication

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

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
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.
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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.

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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)

Moringa oleifera and Curcuma longa versus SARS-CoV-2



J Pharm Pharmacogn Res 10(1): 138-146, 2022.

Original Article

Herbal combination from Moringa oleifera Lam. and Curcuma longa L. as SARS-CoV-2 antiviral via dual inhibitor pathway: A viroinformatics approach

[Combinación de hierbas de Moringa oleifera Lam. y Curcuma longa L. como antiviral SARS-CoV-2 a través de la vía del inhibidor dual: Un enfoque de viroinformática]

Viol Dhea Kharisma1,2#, Aggy Agatha2,3, Arif Nur Muhammad Ansori4#, Muhammad Hermawan Widyananda2,5, Wahyu Choirur Rizky6, Tim Godefridus Antonius Dings7, Marina Derkho8, Irina Lykasova8, Yulanda Antonius9, Imam Rosadi10, Rahadian Zainul11*

1Master Program in Biology, Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, Indonesia.

2Generasi Biologi Indonesia Foundation, Gresik, Indonesia.

3School of Life Sciences and Technology, Bandung Institute of Technology, Bandung, Indonesia.

4Doctoral Program in Veterinary Science, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia.

5Laboratory of Animal Physiology, Structure, and Growth, Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, Indonesia.

6College of Medicine, Sulaiman Al Rajhi University, Al Bukayriyah, Qassim, Saudi Arabia.

7College of Medicine, Maastricht University, Maastricht, The Netherlands.

8Department of Natural Sciences, South-Urals State Agrarian University, Troitsk, Russian Federation.

9Faculty of Biotechnology, University of Surabaya, Surabaya, Indonesia.

10Department of Biology, Faculty of Mathematics and Natural Sciences, Mulawarman University, Samarinda, Indonesia.

11Department of Chemistry, Faculty of Mathematic and Natural Sciences, Universitas Negeri Padang, Padang, Indonesia.

#These authors contributed equally to this work.

*E-mail: rahadianzmsiphd@fmipa.unp.ac.id

Abstract

Context: The COVID-19 outbreak is caused by the transmission and infection of SARS-CoV-2 at the end of 2019. It has led many countries to implement lockdown policies to prevent the viral spreading. Problems arise in a COVID-19 patient because of viral infection that leads to a systemic response in the immune system, specifically due to cytokine storm. Moreover, the antiviral drugs that have not been found. Indonesia had a variety of traditional medicines, such as is ‘jamu’. It consists of a mixture of natural ingredients such as Moringa oleifera Lam. and Curcuma longa L.

Aims: To identify the activity of dual inhibitors as antiviral and anti-inflammatory agents from herbal combination compounds.

Methods: Sample was collected from PubChem (NCBI, USA) and Protein Data Bank (PDB), then drug-likeness analysis using Lipinski rule of five in SCFBIO web server and bioactive probability analysis of bioactive compounds were conducted by PASS web server. Furthermore, the blind docking method was performed using PyRx 0.8 software to determine the binding activity and molecular interaction by PoseView web server and PyMol software v2.4.1 (Schrödinger, Inc, USA).

Results: Cryptochlorogenic acid and curcumin have been computationally proven as dual inhibitors for antivirals by inhibiting Mpro SARS-CoV-2 and as anti-inflammatory through inhibition of NFKB1 activity. However, the results are merely computational so that it must be validated through a wet lab research.

Conclusions: The combination of Moringa oleifera Lam. and Curcuma longa L. is predicted to have antiviral and anti-inflammatory activity through dual inhibitor mechanism played by cryptochlorogenic acid and curcumin.

Keywords: COVID-19; Curcuma longa; Moringa oleifera; Mpro; NFKB1.

Resumen

Contexto: El brote de COVID-19 es causado por la transmisión e infección del SARS-CoV-2. En un paciente con COVID-19 surgen problemas debido a una infección viral que conduce a una respuesta inmunológica sistémica. Además, no se han encontrado medicamentos antivirales. En Indonesia existe una preparación tradicional conocida como el “jamu”. Esta es una mezla de Moringa oleifera Lam. y Curcuma longa L.

Objetivos: Identificar la actividad de inhibidores duales como agentes antivirales y antiinflamatorios de compuestos de combinación de hierbas.

Métodos: Se recogió una muestra de PubChem (NCBI, EE. UU.) y Protein Data Bank (PDB), luego se realizó un análisis de similitud con el fármaco utilizando la regla de cinco de Lipinski en el servidor web SCFBIO y el servidor web PASS realizó un análisis de probabilidad bioactiva de los compuestos bioactivos. Además, el método de acoplamiento ciego se realizó utilizando el software PyRx 0.8 para determinar la actividad de unión y la interacción molecular mediante el servidor web PoseView y el software PyMol v2.4.1 (Schrödinger, Inc, EE. UU.).

Resultados: Se ha comprobado computacionalmente que el ácido criptoclorogénico y la curcumina son inhibidores duales de los antivirales al inhibir el Mpro SARS-CoV-2 y como antiinflamatorios mediante la inhibición de la actividad de NFKB1. Sin embargo, los resultados son meramente computacionales, por lo que deben validarse mediante una investigación de laboratorio húmedo.

Conclusiones: Se predice que la combinación de Moringa oleifera Lam. y Curcuma longa L. tiene actividad antiviral y antiinflamatoria a través de un mecanismo inhibidor dual desempeñado por el ácido criptoclorogénico y la curcumina.

Palabras Clave: COVID-19; Curcuma longa; Moringa oleifera; Mpro; NFKB1.

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Citation Format: 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.

© 2022 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)

Adverse reaction and biosafety of ozone in COVID 19-Cuba



J Pharm Pharmacogn Res 9(4): 465-473, 2021.

Original article

Observancia de reacciones adversas y análisis de cumplimiento de bioseguridad en la aplicación rectal de ozonoterapia en pacientes cubanos con infección aguda o convalecientes de COVID-19

[Observance of adverse reactions and analysis of biosafety compliance in the rectal application of ozone therapy in COVID-19 Cuban patients with acute infection or convalescent]

Lizette Gil del Valle1*, Mario M. Delgado Guerra2, Ana L. Carballo- Reyes3, Joniel A. Sánchez Márquez2, Olga E. López Fernández2, Faustina Fonseca Betancourt2, Zullyt Zamora-Rodríguez3, Lidia A. Fernández García3, Rodolfo Suárez Iznaga4, Raiza Martinez Casanueva4, Lisandra Castro de la Fe4, Niorkidis Gonzalez Carvajal4, Silvia V. Castellanos Veitia4, Yamila R. de Armas-Aguila5

1Departamento de Investigaciones Farmacológicas, Instituto “Pedro Kourí” (IPK), La Habana, Cuba.

2Hospital Ernesto Guevara, Universidad de Ciencias Informáticas, La Habana, Cuba.

3Centro Nacional de Investigaciones Científicas, BioCubaFarma, La Habana, Cuba.

4Hospital Salvador Allende, La Habana, Cuba.

5Ministerio de Salud Pública, La Habana, Cuba.

*E-mail: lgil@ipk.sld.cu

Abstract

Context: Patients with COVID-19 present different biochemical and metabolic alterations from the acute state of infection until months later with variability of symptoms and increased toxicity of drugs related to oxidative stress according to previous studies. There are various alternatives to modulate oxidative stress, including the use of medical ozone, which rectal way requires observing both compliance with biosafety measures and adverse reactions in patients.

Aims: To evaluate compliance with biosafety measures and the possible manifestations of adverse events in the rectal application of ozone therapy in patients with acute infection or convalescent of COVID-19.

Methods: Descriptive, longitudinal studies in two clinical trials conducted at the Ernesto Guevara Hospital and the Salvador Allende Hospital, from May to July 2020. Rectal ozone therapy was applied to patients in two trials with a cycle of up to 20 applications according to the study. The activities were described and the performance of the professionals in the procedure was evaluated through an observation guide. Patient follow-up and surveillance for potential adverse reactions were performed.

Results: 80% (28/36) of the patients reported the feeling of fullness of the intestines, without other reports, in no case treatment was required. The evaluation of the practices showed full compliance with the procedures without transmission of infection during the period.

Conclusions: Compliance with good practices and biosafety in the rectal application of ozone results in the adequate performance of the protocols with benefit and safety for patients under treatment.

Keywords: adverse reactions; biosafety; COVID-19; ozone therapy.

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Resumen

Contexto: En la COVID-19 se presentan diferentes alteraciones bioquímicas y metabólicas desde el estado agudo de infección hasta meses después con variabilidad de síntomas e incremento en la toxicidad a los medicamentos relacionado con el estrés oxidativo según estudios previos. Para modular el estrés oxidativo existen diversas alternativas entre ellas el ozono médico que por vía rectal requiere observar el cumplimiento de las medidas de bioseguridad y de las reacciones adversas en los pacientes.

Objetivos: Evaluar el cumplimiento de la bioseguridad y las posibles manifestaciones de reacciones adversas en la aplicación rectal de ozonoterapia en pacientes con infección aguda o convalecientes de COVID-19.

Métodos: Estudios descriptivos, longitudinales en dos ensayos clínicos realizados en el Hospital Ernesto Guevara y el Hospital Salvador Allende, de mayo a julio de 2020. Se realizó aplicación de ozonoterapia rectal con ciclo de hasta 20 aplicaciones. Se describe y evalúa la ejecución del proceder de los profesionales a través de una guía de observación. Se realizó seguimiento de los pacientes y vigilancia de las reacciones adversas potenciales.

Resultados: Fue referido en el 80% (28/36) de los pacientes la sensación de llenado de los intestinos, sin otros reportes, en ningún caso se requirió tratamiento. La evaluación de las prácticas mostró el cumplimiento en su totalidad de los procedimientos sin transmisión de infección durante el periodo.

Conclusiones: El cumplimiento de los procedimientos y de la bioseguridad en la aplicación rectal de ozono influyen en el desempeño adecuado de los protocolos con beneficio y seguridad para los pacientes en tratamiento.

Palabras Clave: bioseguridad; COVID-19; ozonoterapia; reacciones adversas.

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Citation Format: Gil del Valle L, Delgado Guerra MM, Carballo-Reyes AL, Sánchez Márquez JA, López Fernández OE, Fonseca Betancourt F, Zamora-Rodríguez Z, Fernández García LA, Suárez Iznaga R, Martinez Casanueva R, Castro de la Fe L, Gonzalez Carvajal N, Castellanos Veitia SV, de Armas-Aguila YR (2021) Observancia de reacciones adversas y análisis de cumplimiento de bioseguridad en la aplicación rectal de ozonoterapia en pacientes cubanos con infección aguda o convalecientes de COVID-19 [Observance of adverse reactions and analysis of biosafety compliance in the rectal application of ozone therapy in COVID-19 Cuban patients with acute infection or convalescent]. J Pharm Pharmacogn Res 9(4): 465–473.

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)