Computational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by Grazoprevir

Abstract Outcomes of various clinical studies for the coronavirus disease 2019 (COVID-19) treatment indicated that the drug acts via inhibition of multiple pathways (targets) is likely to be more successful and promising. Keeping this hypothesis intact, the present study describes for the first-time...

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Autores principales:	Santosh Kumar Behera, Nazmina Vhora, Darshan Contractor, Amit Shard, Dinesh Kumar, Kiran Kalia, Alok Jain
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/571d18671e3846828d659367d9803e1d
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spelling	oai:doaj.org-article:571d18671e3846828d659367d9803e1d2021-12-02T14:25:03ZComputational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by Grazoprevir10.1038/s41598-021-86712-22045-2322https://doaj.org/article/571d18671e3846828d659367d9803e1d2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86712-2https://doaj.org/toc/2045-2322Abstract Outcomes of various clinical studies for the coronavirus disease 2019 (COVID-19) treatment indicated that the drug acts via inhibition of multiple pathways (targets) is likely to be more successful and promising. Keeping this hypothesis intact, the present study describes for the first-time, Grazoprevir, an FDA approved anti-viral drug primarily approved for Hepatitis C Virus (HCV), mediated multiple pathway control via synergistic inhibition of viral entry targeting host cell Angiotensin-Converting Enzyme 2 (ACE-2)/transmembrane serine protease 2 (TMPRSS2) and viral replication targeting RNA-dependent RNA polymerase (RdRP). Molecular modeling followed by in-depth structural analysis clearly demonstrated that Grazoprevir interacts with the key residues of these targets. Futher, Molecular Dynamics (MD) simulations showed stability and burial of key residues after the complex formation. Finally, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) analysis identified the governing force of drug-receptor interactions and stability. Thus, we believe that Grazoprevir could be an effective therapeutics for the treatment of the COVID-19 pandemic with a promise of unlikely drug resistance owing to multiple inhibitions of eukaryotic and viral proteins, thus warrants further clinical studies.Santosh Kumar BeheraNazmina VhoraDarshan ContractorAmit ShardDinesh KumarKiran KaliaAlok JainNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Santosh Kumar Behera Nazmina Vhora Darshan Contractor Amit Shard Dinesh Kumar Kiran Kalia Alok Jain Computational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by Grazoprevir
description	Abstract Outcomes of various clinical studies for the coronavirus disease 2019 (COVID-19) treatment indicated that the drug acts via inhibition of multiple pathways (targets) is likely to be more successful and promising. Keeping this hypothesis intact, the present study describes for the first-time, Grazoprevir, an FDA approved anti-viral drug primarily approved for Hepatitis C Virus (HCV), mediated multiple pathway control via synergistic inhibition of viral entry targeting host cell Angiotensin-Converting Enzyme 2 (ACE-2)/transmembrane serine protease 2 (TMPRSS2) and viral replication targeting RNA-dependent RNA polymerase (RdRP). Molecular modeling followed by in-depth structural analysis clearly demonstrated that Grazoprevir interacts with the key residues of these targets. Futher, Molecular Dynamics (MD) simulations showed stability and burial of key residues after the complex formation. Finally, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) analysis identified the governing force of drug-receptor interactions and stability. Thus, we believe that Grazoprevir could be an effective therapeutics for the treatment of the COVID-19 pandemic with a promise of unlikely drug resistance owing to multiple inhibitions of eukaryotic and viral proteins, thus warrants further clinical studies.
format	article
author	Santosh Kumar Behera Nazmina Vhora Darshan Contractor Amit Shard Dinesh Kumar Kiran Kalia Alok Jain
author_facet	Santosh Kumar Behera Nazmina Vhora Darshan Contractor Amit Shard Dinesh Kumar Kiran Kalia Alok Jain
author_sort	Santosh Kumar Behera
title	Computational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by Grazoprevir
title_short	Computational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by Grazoprevir
title_full	Computational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by Grazoprevir
title_fullStr	Computational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by Grazoprevir
title_full_unstemmed	Computational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by Grazoprevir
title_sort	computational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by grazoprevir
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/571d18671e3846828d659367d9803e1d
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Computational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by Grazoprevir

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