Discovery of New Hydroxyethylamine Analogs against 3CL(pro) Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studies

Detalhes bibliográficos
Autor(a) principal: Kumar S
Data de Publicação: 2020
Outros Autores: Sharma PP, Shankar U, Kumar D, Joshi SK, Pena L, Durvasula R, Kumar A, Kempaiah P, Poonam, Rathi B.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/58148
Resumo: Fundação Oswaldo Cruz, Instituto Aggeu Magalhães, Departamento de Virologia, Recife, PE, Brasil. University of Delhi, Department of Chemistry, Miranda House, India. University of Delhi, Hansraj College, Laboratory for Translational Chemistry and Drug Discovery, India. Indian Institute of Technology, Descipline of Bioscience and Biomedical Engineering, Indore India. Amity University Uttar Pradesh, Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), India. Technology Advisor, Defence Research & Development Organization, Rajaji Marg, New Delhi, India. Loyola University Stritch School of Medicine, Department of Medicine, Chicago, United States.
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spelling Kumar SSharma PPShankar UKumar DJoshi SKPena LDurvasula RKumar AKempaiah PPoonamRathi B.2023-05-05T15:25:22Z2023-05-05T15:25:22Z2020KUMAR, Sumit; SHARMA, Prem Prakash; SHANKAR, Uma; KUMAR, Dhruv; JOSHI, Sanjeev K.; PENA, Lindomar; DURVASULA, Ravi; KUMAR, Amit; KEMPAIAH, Prakasha; POONAM. Discovery of New Hydroxyethylamine Analogs against 3CLpro Protein Target of SARS-CoV-2: molecular docking, molecular dynamics simulation, and structure⠳activity relationship studies. Journal Of Chemical Information And Modeling, [S.L.], v. 60, n. 12, p. 5754-5770, 2 jun. 2020. American Chemical Society (ACS). http://dx.doi.org/10.1021/acs.jcim.0c00326.1549-960Xhttps://www.arca.fiocruz.br/handle/icict/5814810.1021/acs.jcim.0c00326engDiscovery of New Hydroxyethylamine Analogs against 3CL(pro) Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studiesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz, Instituto Aggeu Magalhães, Departamento de Virologia, Recife, PE, Brasil. University of Delhi, Department of Chemistry, Miranda House, India. University of Delhi, Hansraj College, Laboratory for Translational Chemistry and Drug Discovery, India. Indian Institute of Technology, Descipline of Bioscience and Biomedical Engineering, Indore India. Amity University Uttar Pradesh, Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), India. Technology Advisor, Defence Research & Development Organization, Rajaji Marg, New Delhi, India. Loyola University Stritch School of Medicine, Department of Medicine, Chicago, United States.Discovery of New Hydroxyethylamine Analogs against 3CLpro Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure−Activity Relationship Studies Sumit Kumar,○ Prem Prakash Sharma,○ Uma Shankar, Dhruv Kumar, Sanjeev K. Joshi, Lindomar Pena, Ravi Durvasula, Amit Kumar, Prakasha Kempaiah, Poonam,* and Brijesh Rathi* Cite This: J. Chem. Inf. Model. 2020, 60, 5754−5770 Read Online ACCESS Metrics & More Article Recommendations *sı Supporting Information ABSTRACT: The novel coronavirus, SARS-CoV-2, has caused a recent pandemic called COVID-19 and a severe health threat around the world. In the current situation, the virus is rapidly spreading worldwide, and the discovery of a vaccine and potential therapeutics are critically essential. The crystal structure for the main protease (Mpro ) of SARS-CoV-2, 3-chymotrypsin-like cysteine protease (3CL pro ), was recently made available and is considerably similar to the previously reported SARS-CoV. Due to its essentiality in viral replication, it represents a potential drug target. Herein, a computer-aided drug design (CADD) approach was implemented for the initial screening of 13 approved antiviral drugs. Molecular docking of 13 antivirals against the 3-chymotrypsin- like cysteine protease (3CLpro ) enzyme was accomplished, and indinavir was described as a lead drug with a docking score of −8.824 and a XP Gscore of −9.466 kcal/mol. Indinavir possesses an important pharmacophore, hydroxyethylamine (HEA), and thus, a new library of HEA compounds (>2500) was subjected to virtual screening that led to 25 hits with a docking score more than indinavir. Exclusively, compound 16 with a docking score of −8.955 adhered to drug-like parameters, and the structure−activity relationship (SAR) analysis was demonstrated to highlight the importance of chemical scaffolds therein. Molecular dynamics (MD) simulation analysis performed at 100 ns supported the stability of 16 within the binding pocket. Largely, our results supported that this novel compound 16 binds with domains I and II, and the domain II−III linker of the 3CLpro protein, suggesting its suitability as a strong candidate for therapeutic discovery against COVID-19.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALDiscovery of New Hydroxyethylamine Analogs against 3CLpro.pdfDiscovery of New Hydroxyethylamine Analogs against 3CLpro.pdfapplication/pdf8234839https://www.arca.fiocruz.br/bitstream/icict/58148/3/Discovery%20of%20New%20Hydroxyethylamine%20Analogs%20against%203CLpro.pdf4d78eb43dd2c1b47b2d42c0d33f6e58dMD53LICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/58148/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51icict/581482023-05-15 12:26:26.561oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-05-15T15:26:26Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Discovery of New Hydroxyethylamine Analogs against 3CL(pro) Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studies
title Discovery of New Hydroxyethylamine Analogs against 3CL(pro) Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studies
spellingShingle Discovery of New Hydroxyethylamine Analogs against 3CL(pro) Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studies
Kumar S
title_short Discovery of New Hydroxyethylamine Analogs against 3CL(pro) Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studies
title_full Discovery of New Hydroxyethylamine Analogs against 3CL(pro) Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studies
title_fullStr Discovery of New Hydroxyethylamine Analogs against 3CL(pro) Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studies
title_full_unstemmed Discovery of New Hydroxyethylamine Analogs against 3CL(pro) Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studies
title_sort Discovery of New Hydroxyethylamine Analogs against 3CL(pro) Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studies
author Kumar S
author_facet Kumar S
Sharma PP
Shankar U
Kumar D
Joshi SK
Pena L
Durvasula R
Kumar A
Kempaiah P
Poonam
Rathi B.
author_role author
author2 Sharma PP
Shankar U
Kumar D
Joshi SK
Pena L
Durvasula R
Kumar A
Kempaiah P
Poonam
Rathi B.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Kumar S
Sharma PP
Shankar U
Kumar D
Joshi SK
Pena L
Durvasula R
Kumar A
Kempaiah P
Poonam
Rathi B.
description Fundação Oswaldo Cruz, Instituto Aggeu Magalhães, Departamento de Virologia, Recife, PE, Brasil. University of Delhi, Department of Chemistry, Miranda House, India. University of Delhi, Hansraj College, Laboratory for Translational Chemistry and Drug Discovery, India. Indian Institute of Technology, Descipline of Bioscience and Biomedical Engineering, Indore India. Amity University Uttar Pradesh, Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), India. Technology Advisor, Defence Research & Development Organization, Rajaji Marg, New Delhi, India. Loyola University Stritch School of Medicine, Department of Medicine, Chicago, United States.
publishDate 2020
dc.date.issued.fl_str_mv 2020
dc.date.accessioned.fl_str_mv 2023-05-05T15:25:22Z
dc.date.available.fl_str_mv 2023-05-05T15:25:22Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv KUMAR, Sumit; SHARMA, Prem Prakash; SHANKAR, Uma; KUMAR, Dhruv; JOSHI, Sanjeev K.; PENA, Lindomar; DURVASULA, Ravi; KUMAR, Amit; KEMPAIAH, Prakasha; POONAM. Discovery of New Hydroxyethylamine Analogs against 3CLpro Protein Target of SARS-CoV-2: molecular docking, molecular dynamics simulation, and structure⠳activity relationship studies. Journal Of Chemical Information And Modeling, [S.L.], v. 60, n. 12, p. 5754-5770, 2 jun. 2020. American Chemical Society (ACS). http://dx.doi.org/10.1021/acs.jcim.0c00326.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/58148
dc.identifier.issn.en_US.fl_str_mv 1549-960X
dc.identifier.doi.none.fl_str_mv 10.1021/acs.jcim.0c00326
identifier_str_mv KUMAR, Sumit; SHARMA, Prem Prakash; SHANKAR, Uma; KUMAR, Dhruv; JOSHI, Sanjeev K.; PENA, Lindomar; DURVASULA, Ravi; KUMAR, Amit; KEMPAIAH, Prakasha; POONAM. Discovery of New Hydroxyethylamine Analogs against 3CLpro Protein Target of SARS-CoV-2: molecular docking, molecular dynamics simulation, and structure⠳activity relationship studies. Journal Of Chemical Information And Modeling, [S.L.], v. 60, n. 12, p. 5754-5770, 2 jun. 2020. American Chemical Society (ACS). http://dx.doi.org/10.1021/acs.jcim.0c00326.
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