Discovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARSCoV-2: Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies

Detalhes bibliográficos
Autor(a) principal: Kumar, Sumit
Data de Publicação: 2020
Outros Autores: Sharma, Prem Prakash, Shankar, Uma, Kumar, Dhruv, Joshi, Sanjeev K., Pena, Lindomar José, Durvasula, Ravi, Kumar, Amit, Kempaiah, Prakasha, Poonam, Rathi, Brijesh
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/42005
Resumo: University of Delhi. Miranda House. Department of Chemistry. Delhi, India.
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spelling Kumar, SumitSharma, Prem PrakashShankar, UmaKumar, DhruvJoshi, Sanjeev K.Pena, Lindomar JoséDurvasula, RaviKumar, AmitKempaiah, PrakashaPoonamRathi, Brijesh2020-06-30T16:16:12Z2020-06-30T16:16:12Z2020KUMAR, Sumit et al. University of Delhi. Hansraj College. Laboratory for Translational Chemistry and Drug Discovery. Delhi, India. Jornal of Medical Information and Modeling, p. 1-17, 2020.1549-9596https://www.arca.fiocruz.br/handle/icict/4200510.1021/acs.jcim.0c00326engAmerican Chemical Societyhttps://www.arca.fiocruz.br/handle/icict/42281Discovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARSCoV-2: Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studiesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversity of Delhi. Miranda House. Department of Chemistry. Delhi, India.University of Delhi. Hansraj College. Laboratory for Translational Chemistry and Drug Discovery. Delhi, India.Indian Institute of Technology. Descipline of Bioscience and Biomedical Engineering. Indore, Simrol, India.Amity University Uttar Pradesh, Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR). Sec-125. Noida, India.Defence Research & Development Organization, HQ, Rajaji Marg, New Delhi, India.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Loyola University Stritch School of Medicine. Department of Medicine. Chicago, Illinois, USA.University of Delhi. Miranda House. Department of Chemistry. Delhi, India.University of Delhi. Hansraj College. Laboratory for Translational Chemistry and Drug Discovery. Delhi, India.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 (3CLpro), 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.CoronavirusCOVID-19Quick TestSARS-CoV-2Virtual screeningHydroxyethylamineMolecular Docking ApproachesMolecular Dynamics Simulationinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83132https://www.arca.fiocruz.br/bitstream/icict/42005/1/license.txt70425d8cb6e40fdcf4edd2ef0660b45bMD51ORIGINALDiscovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARS-CoV-2 Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies.pdfDiscovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARS-CoV-2 Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies.pdfArtigoapplication/pdf1995268https://www.arca.fiocruz.br/bitstream/icict/42005/2/Discovery%20of%20New%20Hydroxyethylamine%20Analogs%20Against%203CLpro%20Protein%20Target%20of%20SARS-CoV-2%20Molecular%20Docking%2c%20Molecular%20Dynamics%20Simulation%20and%20Structure-Activity%20Relationship%20Studies.pdfb55cb331bb915ca546c3d66e19c62b7bMD52Supporting Information.pdfSupporting Information.pdfMaterial Suplementarapplication/pdf640068https://www.arca.fiocruz.br/bitstream/icict/42005/3/Supporting%20Information.pdf6666f90d7d540af81aa167b707544e28MD53TEXTDiscovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARS-CoV-2 Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies.pdf.txtDiscovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARS-CoV-2 Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies.pdf.txtExtracted 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dc.title.en.fl_str_mv Discovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARSCoV-2: Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies
title Discovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARSCoV-2: Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies
spellingShingle Discovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARSCoV-2: Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies
Kumar, Sumit
Coronavirus
COVID-19
Quick Test
SARS-CoV-2
Virtual screening
Hydroxyethylamine
Molecular Docking Approaches
Molecular Dynamics Simulation
title_short Discovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARSCoV-2: Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies
title_full Discovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARSCoV-2: Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies
title_fullStr Discovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARSCoV-2: Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies
title_full_unstemmed Discovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARSCoV-2: Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies
title_sort Discovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARSCoV-2: Molecular Docking, Molecular Dynamics Simulation and Structure-Activity Relationship Studies
author Kumar, Sumit
author_facet Kumar, Sumit
Sharma, Prem Prakash
Shankar, Uma
Kumar, Dhruv
Joshi, Sanjeev K.
Pena, Lindomar José
Durvasula, Ravi
Kumar, Amit
Kempaiah, Prakasha
Poonam
Rathi, Brijesh
author_role author
author2 Sharma, Prem Prakash
Shankar, Uma
Kumar, Dhruv
Joshi, Sanjeev K.
Pena, Lindomar José
Durvasula, Ravi
Kumar, Amit
Kempaiah, Prakasha
Poonam
Rathi, Brijesh
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Kumar, Sumit
Sharma, Prem Prakash
Shankar, Uma
Kumar, Dhruv
Joshi, Sanjeev K.
Pena, Lindomar José
Durvasula, Ravi
Kumar, Amit
Kempaiah, Prakasha
Poonam
Rathi, Brijesh
dc.subject.en.en.fl_str_mv Coronavirus
COVID-19
Quick Test
SARS-CoV-2
Virtual screening
Hydroxyethylamine
Molecular Docking Approaches
Molecular Dynamics Simulation
topic Coronavirus
COVID-19
Quick Test
SARS-CoV-2
Virtual screening
Hydroxyethylamine
Molecular Docking Approaches
Molecular Dynamics Simulation
description University of Delhi. Miranda House. Department of Chemistry. Delhi, India.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-06-30T16:16:12Z
dc.date.available.fl_str_mv 2020-06-30T16:16:12Z
dc.date.issued.fl_str_mv 2020
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 et al. University of Delhi. Hansraj College. Laboratory for Translational Chemistry and Drug Discovery. Delhi, India. Jornal of Medical Information and Modeling, p. 1-17, 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/42005
dc.identifier.issn.pt_BR.fl_str_mv 1549-9596
dc.identifier.doi.pt_BR.fl_str_mv 10.1021/acs.jcim.0c00326
identifier_str_mv KUMAR, Sumit et al. University of Delhi. Hansraj College. Laboratory for Translational Chemistry and Drug Discovery. Delhi, India. Jornal of Medical Information and Modeling, p. 1-17, 2020.
1549-9596
10.1021/acs.jcim.0c00326
url https://www.arca.fiocruz.br/handle/icict/42005
dc.language.iso.fl_str_mv eng
language eng
dc.relation.hasversion.pt_BR.fl_str_mv https://www.arca.fiocruz.br/handle/icict/42281
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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https://www.arca.fiocruz.br/bitstream/icict/42005/3/Supporting%20Information.pdf
https://www.arca.fiocruz.br/bitstream/icict/42005/4/Discovery%20of%20New%20Hydroxyethylamine%20Analogs%20Against%203CLpro%20Protein%20Target%20of%20SARS-CoV-2%20Molecular%20Docking%2c%20Molecular%20Dynamics%20Simulation%20and%20Structure-Activity%20Relationship%20Studies.pdf.txt
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