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Computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in COVID-19
Bioflavonoids are the largest group of plant-derived polyphenolic compounds with diverse biological potential and have also been proven efficacious in the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The present investigation validates molecular...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Authors. Published by Elsevier Ltd.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756171/ https://www.ncbi.nlm.nih.gov/pubmed/33363251 http://dx.doi.org/10.1016/j.imu.2020.100504 |
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author | Patil, Rajesh Chikhale, Rupesh Khanal, Pukar Gurav, Nilambari Ayyanar, Muniappan Sinha, Saurabh Prasad, Satyendra Dey, Yadu Nandan Wanjari, Manish Gurav, Shailendra S. |
author_facet | Patil, Rajesh Chikhale, Rupesh Khanal, Pukar Gurav, Nilambari Ayyanar, Muniappan Sinha, Saurabh Prasad, Satyendra Dey, Yadu Nandan Wanjari, Manish Gurav, Shailendra S. |
author_sort | Patil, Rajesh |
collection | PubMed |
description | Bioflavonoids are the largest group of plant-derived polyphenolic compounds with diverse biological potential and have also been proven efficacious in the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The present investigation validates molecular docking, simulation, and MM-PBSA studies of fifteen bioactive bioflavonoids derived from plants as a plausible potential antiviral in the treatment of COVID-19. Molecular docking studies for 15 flavonoids on the three SARS CoV-2 proteins, non-structural protein-15 Endoribonuclease (NSP15), the receptor-binding domain of spike protein (RBD of S protein), and main protease (M(pro)/3CL(pro)) were performed and selected protein-ligand complexes were subjected to Molecular Dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-PBSA method. All flavonoids were further assessed for their effectiveness as adjuvant therapy by network pharmacology analysis on the target proteins. The network pharmacology analysis suggests the involvement of selected bioflavonoids in the modulation of multiple signaling pathways like p53, FoxO, MAPK, Wnt, Rap1, TNF, adipocytokine, and leukocyte transendothelial migration which plays a significant role in immunomodulation, minimizing the oxidative stress and inflammation. Molecular docking and molecular dynamics simulation studies illustrated the potential of glycyrrhizic acid, amentoflavone, and mulberroside in inhibiting key SARS-CoV-2 proteins and these results could be exploited further in designing future ligands from natural sources. |
format | Online Article Text |
id | pubmed-7756171 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Authors. Published by Elsevier Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77561712020-12-23 Computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in COVID-19 Patil, Rajesh Chikhale, Rupesh Khanal, Pukar Gurav, Nilambari Ayyanar, Muniappan Sinha, Saurabh Prasad, Satyendra Dey, Yadu Nandan Wanjari, Manish Gurav, Shailendra S. Inform Med Unlocked Article Bioflavonoids are the largest group of plant-derived polyphenolic compounds with diverse biological potential and have also been proven efficacious in the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The present investigation validates molecular docking, simulation, and MM-PBSA studies of fifteen bioactive bioflavonoids derived from plants as a plausible potential antiviral in the treatment of COVID-19. Molecular docking studies for 15 flavonoids on the three SARS CoV-2 proteins, non-structural protein-15 Endoribonuclease (NSP15), the receptor-binding domain of spike protein (RBD of S protein), and main protease (M(pro)/3CL(pro)) were performed and selected protein-ligand complexes were subjected to Molecular Dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-PBSA method. All flavonoids were further assessed for their effectiveness as adjuvant therapy by network pharmacology analysis on the target proteins. The network pharmacology analysis suggests the involvement of selected bioflavonoids in the modulation of multiple signaling pathways like p53, FoxO, MAPK, Wnt, Rap1, TNF, adipocytokine, and leukocyte transendothelial migration which plays a significant role in immunomodulation, minimizing the oxidative stress and inflammation. Molecular docking and molecular dynamics simulation studies illustrated the potential of glycyrrhizic acid, amentoflavone, and mulberroside in inhibiting key SARS-CoV-2 proteins and these results could be exploited further in designing future ligands from natural sources. The Authors. Published by Elsevier Ltd. 2021 2020-12-23 /pmc/articles/PMC7756171/ /pubmed/33363251 http://dx.doi.org/10.1016/j.imu.2020.100504 Text en © 2020 The Authors Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Patil, Rajesh Chikhale, Rupesh Khanal, Pukar Gurav, Nilambari Ayyanar, Muniappan Sinha, Saurabh Prasad, Satyendra Dey, Yadu Nandan Wanjari, Manish Gurav, Shailendra S. Computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in COVID-19 |
title | Computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in COVID-19 |
title_full | Computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in COVID-19 |
title_fullStr | Computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in COVID-19 |
title_full_unstemmed | Computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in COVID-19 |
title_short | Computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in COVID-19 |
title_sort | computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in covid-19 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756171/ https://www.ncbi.nlm.nih.gov/pubmed/33363251 http://dx.doi.org/10.1016/j.imu.2020.100504 |
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