Discovery of new hydroxyethylamine analogs against 3CLpro protein target of SARS-CoV-2: molecular docking, molecular dynamics simulation, and structure−activity relationship studies
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/42281 |
Resumo: | Articles ASAP (Computational Chemistry). ASAP Articles are edited and published online ahead of issue. |
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Kumar, SumitSharma, Prem PrakashShankar, UmaKumar, DhruvJoshi, Sanjeev K.Pena, Lindomar JoséDurvasula, RaviKumar, AmitKempaiah, PrakashaPoonamRathi, Brijesh2020-07-16T14:47:21Z2020-07-16T14:47:21Z2020KUMAR, Sumit et al. 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, p. 1-17, 2 Jun. 2020.1549-9596https://www.arca.fiocruz.br/handle/icict/4228110.1021/acs.jcim.0c003261549-960XArticles ASAP (Computational Chemistry). ASAP Articles are edited and published online ahead of issue.University of Delhi. Miranda House. Department of Chemistry. New Delhi, Delhi, India.University of Delhi. Hansraj College. Laboratory For Translational Chemistry and Drug Discovery. Malka Ganj, Delhi, India.Indian Institute of Technology. Department of Biosciences and Biomedical Engineering. Simrol, Indore, India.Amity University. Amity Institute of Molecular Medicine & Stem Cell Research. Noida, Uttar Pradesh, India.Defence Research and Development Organisation. New Delhi, Delhi, India.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Virologia e Terapia Experimental. Recife, PE, Brasil.Loyola University. Stritch School of Medicine. Department of Medicine. Maywood, Illinois, USA.Indian Institute of Technology. Department of Biosciences and Biomedical Engineering. Simrol, Indore, India.Loyola University. Stritch School of Medicine. Department of Medicine. Maywood, Illinois, USA.University of Delhi. Miranda House. Department of Chemistry. New Delhi, Delhi, India.University of Delhi. Hansraj College. Laboratory For Translational Chemistry and Drug Discovery. Malka Ganj, 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.engAmerican Chemical Societyhttps://www.arca.fiocruz.br/handle/icict/42005Discovery of new hydroxyethylamine analogs against 3CLpro protein target of SARS-CoV-2: molecular docking, molecular dynamics simulation, and structure−activity relationship studiesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleAntimicrobial agentsPeptides and proteinsLigandsProtein structureTherapeuticsSARS-CoV-2COVID-19info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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| dc.title.pt_BR.fl_str_mv |
Discovery of new hydroxyethylamine analogs against 3CLpro protein target of SARS-CoV-2: molecular docking, molecular dynamics simulation, and structure−activity relationship studies |
| title |
Discovery of new hydroxyethylamine analogs against 3CLpro protein target of SARS-CoV-2: molecular docking, molecular dynamics simulation, and structure−activity relationship studies |
| spellingShingle |
Discovery of new hydroxyethylamine analogs against 3CLpro protein target of SARS-CoV-2: molecular docking, molecular dynamics simulation, and structure−activity relationship studies Kumar, Sumit Antimicrobial agents Peptides and proteins Ligands Protein structure Therapeutics SARS-CoV-2 COVID-19 |
| title_short |
Discovery of new hydroxyethylamine analogs against 3CLpro protein target of SARS-CoV-2: molecular docking, molecular dynamics simulation, and structure−activity relationship studies |
| title_full |
Discovery of new hydroxyethylamine analogs against 3CLpro protein target of SARS-CoV-2: molecular docking, molecular dynamics simulation, and structure−activity relationship studies |
| title_fullStr |
Discovery of new hydroxyethylamine analogs against 3CLpro 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 3CLpro protein target of SARS-CoV-2: molecular docking, molecular dynamics simulation, and structure−activity relationship studies |
| title_sort |
Discovery of new hydroxyethylamine analogs against 3CLpro protein target of SARS-CoV-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 |
Antimicrobial agents Peptides and proteins Ligands Protein structure Therapeutics SARS-CoV-2 COVID-19 |
| topic |
Antimicrobial agents Peptides and proteins Ligands Protein structure Therapeutics SARS-CoV-2 COVID-19 |
| description |
Articles ASAP (Computational Chemistry). ASAP Articles are edited and published online ahead of issue. |
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2020 |
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2020-07-16T14:47:21Z |
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2020-07-16T14:47:21Z |
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2020 |
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info:eu-repo/semantics/publishedVersion |
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KUMAR, Sumit et al. 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, p. 1-17, 2 Jun. 2020. |
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https://www.arca.fiocruz.br/handle/icict/42281 |
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1549-9596 |
| dc.identifier.doi.pt_BR.fl_str_mv |
10.1021/acs.jcim.0c00326 |
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1549-960X |
| identifier_str_mv |
KUMAR, Sumit et al. 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, p. 1-17, 2 Jun. 2020. 1549-9596 10.1021/acs.jcim.0c00326 1549-960X |
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American Chemical Society |
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