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Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19

The ongoing COVID-19 pandemic has affected millions of people worldwide and caused substantial socio-economic losses. Few successful vaccine candidates have been approved against SARS-CoV-2; however, their therapeutic efficacy against the mutated strains of the virus remains questionable. Furthermor...

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Autores principales: Parihar, Arpana, Sonia, Zannatul Ferdous, Akter, Farjana, Ali, Md Ackas, Hakim, Fuad Taufiqul, Hossain, Md Shahadat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964014/
https://www.ncbi.nlm.nih.gov/pubmed/35390745
http://dx.doi.org/10.1016/j.compbiomed.2022.105468
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author Parihar, Arpana
Sonia, Zannatul Ferdous
Akter, Farjana
Ali, Md Ackas
Hakim, Fuad Taufiqul
Hossain, Md Shahadat
author_facet Parihar, Arpana
Sonia, Zannatul Ferdous
Akter, Farjana
Ali, Md Ackas
Hakim, Fuad Taufiqul
Hossain, Md Shahadat
author_sort Parihar, Arpana
collection PubMed
description The ongoing COVID-19 pandemic has affected millions of people worldwide and caused substantial socio-economic losses. Few successful vaccine candidates have been approved against SARS-CoV-2; however, their therapeutic efficacy against the mutated strains of the virus remains questionable. Furthermore, the limited supply of vaccines and promising antiviral drugs have created havoc in the present scenario. Plant-based phytochemicals (bioactive molecules) are promising because of their low side effects and high therapeutic value. In this study, we aimed to screen for suitable phytochemicals with higher therapeutic value using the two most crucial proteins of SARS-CoV-2, the RNA-dependent RNA polymerase (RdRp) and main protease (Mpro). We used computational tools such as molecular docking and steered molecular dynamics simulations to gain insights into the different types of interactions and estimated the relative binding forces between the phytochemicals and their respective targets. To the best of our knowledge, this is the first report that not only involves a search for a therapeutic bioactive molecule but also sheds light on the mechanisms underlying target inhibition in terms of calculations of force and work needed to extractthe ligand from the pocket of its target. The complexes showing higher binding forces were subjected to 200 ns molecular dynamic simulations to check the stability of the ligand inside the binding pocket. Our results suggested that isoskimmiwallin and terflavin A are potential inhibitors of RdRp, whereas isoquercitrin and isoorientin are the lead molecules against Mpro. Collectively, our findings could potentially aid in the development of novel therapeutics against COVID-19.
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spelling pubmed-89640142022-03-30 Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19 Parihar, Arpana Sonia, Zannatul Ferdous Akter, Farjana Ali, Md Ackas Hakim, Fuad Taufiqul Hossain, Md Shahadat Comput Biol Med Article The ongoing COVID-19 pandemic has affected millions of people worldwide and caused substantial socio-economic losses. Few successful vaccine candidates have been approved against SARS-CoV-2; however, their therapeutic efficacy against the mutated strains of the virus remains questionable. Furthermore, the limited supply of vaccines and promising antiviral drugs have created havoc in the present scenario. Plant-based phytochemicals (bioactive molecules) are promising because of their low side effects and high therapeutic value. In this study, we aimed to screen for suitable phytochemicals with higher therapeutic value using the two most crucial proteins of SARS-CoV-2, the RNA-dependent RNA polymerase (RdRp) and main protease (Mpro). We used computational tools such as molecular docking and steered molecular dynamics simulations to gain insights into the different types of interactions and estimated the relative binding forces between the phytochemicals and their respective targets. To the best of our knowledge, this is the first report that not only involves a search for a therapeutic bioactive molecule but also sheds light on the mechanisms underlying target inhibition in terms of calculations of force and work needed to extractthe ligand from the pocket of its target. The complexes showing higher binding forces were subjected to 200 ns molecular dynamic simulations to check the stability of the ligand inside the binding pocket. Our results suggested that isoskimmiwallin and terflavin A are potential inhibitors of RdRp, whereas isoquercitrin and isoorientin are the lead molecules against Mpro. Collectively, our findings could potentially aid in the development of novel therapeutics against COVID-19. Elsevier Ltd. 2022-06 2022-03-30 /pmc/articles/PMC8964014/ /pubmed/35390745 http://dx.doi.org/10.1016/j.compbiomed.2022.105468 Text en © 2022 Elsevier Ltd. All rights reserved. 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
Parihar, Arpana
Sonia, Zannatul Ferdous
Akter, Farjana
Ali, Md Ackas
Hakim, Fuad Taufiqul
Hossain, Md Shahadat
Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19
title Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19
title_full Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19
title_fullStr Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19
title_full_unstemmed Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19
title_short Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19
title_sort phytochemicals-based targeting rdrp and main protease of sars-cov-2 using docking and steered molecular dynamic simulation: a promising therapeutic approach for tackling covid-19
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964014/
https://www.ncbi.nlm.nih.gov/pubmed/35390745
http://dx.doi.org/10.1016/j.compbiomed.2022.105468
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