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Repurposing FDA-approved phytomedicines, natural products, antivirals and cell protectives against SARS-CoV-2 (COVID-19) RNA-dependent RNA polymerase

Following the recent emergence of SARS-CoV-2 or coronavirus disease 2019 (COVID-19), drug discovery and vaccine design to combat this fatal infection are critical. In this study, an essential enzyme in the SARS-CoV-2 replication machinery, RNA-dependent RNA polymerase (RDRP), is targeted in a virtua...

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Autores principales: Kandeel, Mahmoud, Kitade, Yukio, Almubarak, Abdullah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713599/
https://www.ncbi.nlm.nih.gov/pubmed/33335812
http://dx.doi.org/10.7717/peerj.10480
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author Kandeel, Mahmoud
Kitade, Yukio
Almubarak, Abdullah
author_facet Kandeel, Mahmoud
Kitade, Yukio
Almubarak, Abdullah
author_sort Kandeel, Mahmoud
collection PubMed
description Following the recent emergence of SARS-CoV-2 or coronavirus disease 2019 (COVID-19), drug discovery and vaccine design to combat this fatal infection are critical. In this study, an essential enzyme in the SARS-CoV-2 replication machinery, RNA-dependent RNA polymerase (RDRP), is targeted in a virtual screening assay using a set of 1,664 FDA-approved drugs, including sets of botanical and synthetic derivatives. A set of 22 drugs showed a high docking score of >−7. Notably, approximately one-third of the top hits were either from natural products or biological molecules. The FDA-approved phytochemicals were sennosides, digoxin, asiaticoside, glycyrrhizin, neohesperidin, taxifolin, quercetin and aloin. These approved natural products and phytochemicals are used as general tonics, antioxidants, cell protectives, and immune stimulants (nadid, thymopentin, asiaticoside, glycyrrhizin) and in other miscellaneous systemic or topical applications. A comprehensive analysis was conducted on standard precision and extra precision docking, two-step molecular dynamics simulations, binding energy calculations and a post dynamics analysis. The results reveal that two drugs, docetaxel and neohesperidin, showed strong binding profiles with SARS CoV-2 RdRP. These results can be used as a primer for further drug discovery studies in the treatment of COVID-19. This initiative repurposes safe FDA-approved drugs against COVID-19 RdRP, providing a rapid channel for the discovery and application of new anti-CoV therapeutics.
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spelling pubmed-77135992020-12-16 Repurposing FDA-approved phytomedicines, natural products, antivirals and cell protectives against SARS-CoV-2 (COVID-19) RNA-dependent RNA polymerase Kandeel, Mahmoud Kitade, Yukio Almubarak, Abdullah PeerJ Computational Biology Following the recent emergence of SARS-CoV-2 or coronavirus disease 2019 (COVID-19), drug discovery and vaccine design to combat this fatal infection are critical. In this study, an essential enzyme in the SARS-CoV-2 replication machinery, RNA-dependent RNA polymerase (RDRP), is targeted in a virtual screening assay using a set of 1,664 FDA-approved drugs, including sets of botanical and synthetic derivatives. A set of 22 drugs showed a high docking score of >−7. Notably, approximately one-third of the top hits were either from natural products or biological molecules. The FDA-approved phytochemicals were sennosides, digoxin, asiaticoside, glycyrrhizin, neohesperidin, taxifolin, quercetin and aloin. These approved natural products and phytochemicals are used as general tonics, antioxidants, cell protectives, and immune stimulants (nadid, thymopentin, asiaticoside, glycyrrhizin) and in other miscellaneous systemic or topical applications. A comprehensive analysis was conducted on standard precision and extra precision docking, two-step molecular dynamics simulations, binding energy calculations and a post dynamics analysis. The results reveal that two drugs, docetaxel and neohesperidin, showed strong binding profiles with SARS CoV-2 RdRP. These results can be used as a primer for further drug discovery studies in the treatment of COVID-19. This initiative repurposes safe FDA-approved drugs against COVID-19 RdRP, providing a rapid channel for the discovery and application of new anti-CoV therapeutics. PeerJ Inc. 2020-11-30 /pmc/articles/PMC7713599/ /pubmed/33335812 http://dx.doi.org/10.7717/peerj.10480 Text en © 2020 Kandeel et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Computational Biology
Kandeel, Mahmoud
Kitade, Yukio
Almubarak, Abdullah
Repurposing FDA-approved phytomedicines, natural products, antivirals and cell protectives against SARS-CoV-2 (COVID-19) RNA-dependent RNA polymerase
title Repurposing FDA-approved phytomedicines, natural products, antivirals and cell protectives against SARS-CoV-2 (COVID-19) RNA-dependent RNA polymerase
title_full Repurposing FDA-approved phytomedicines, natural products, antivirals and cell protectives against SARS-CoV-2 (COVID-19) RNA-dependent RNA polymerase
title_fullStr Repurposing FDA-approved phytomedicines, natural products, antivirals and cell protectives against SARS-CoV-2 (COVID-19) RNA-dependent RNA polymerase
title_full_unstemmed Repurposing FDA-approved phytomedicines, natural products, antivirals and cell protectives against SARS-CoV-2 (COVID-19) RNA-dependent RNA polymerase
title_short Repurposing FDA-approved phytomedicines, natural products, antivirals and cell protectives against SARS-CoV-2 (COVID-19) RNA-dependent RNA polymerase
title_sort repurposing fda-approved phytomedicines, natural products, antivirals and cell protectives against sars-cov-2 (covid-19) rna-dependent rna polymerase
topic Computational Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713599/
https://www.ncbi.nlm.nih.gov/pubmed/33335812
http://dx.doi.org/10.7717/peerj.10480
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