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Computational studies indicated the effectiveness of human metabolites against SARS-Cov-2 main protease

To fight against the devastating coronavirus disease 2019 (COVID-19), identifying robust anti-SARS-CoV-2 therapeutics from all possible directions is necessary. To contribute to this effort, we selected a human metabolites database containing waters and lipid-soluble metabolites to screen against th...

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Autores principales: Roy, Rajarshi, Sk, Md Fulbabu, Tanwar, Omprakash, Kar, Parimal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385416/
https://www.ncbi.nlm.nih.gov/pubmed/35978064
http://dx.doi.org/10.1007/s11030-022-10513-6
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author Roy, Rajarshi
Sk, Md Fulbabu
Tanwar, Omprakash
Kar, Parimal
author_facet Roy, Rajarshi
Sk, Md Fulbabu
Tanwar, Omprakash
Kar, Parimal
author_sort Roy, Rajarshi
collection PubMed
description To fight against the devastating coronavirus disease 2019 (COVID-19), identifying robust anti-SARS-CoV-2 therapeutics from all possible directions is necessary. To contribute to this effort, we selected a human metabolites database containing waters and lipid-soluble metabolites to screen against the 3-chymotrypsin-like proteases (3CL(pro)) protein of SARS-CoV-2. The top 8 hits from virtual screening displayed a docking score varying between ~ − 11 and ~ − 14 kcal/mol. Molecular dynamics simulations complement the virtual screening study in conjunction with the molecular mechanics generalized Born surface area (MM/GBSA) scheme. Our analyses revealed that (HMDB0132640) has the best glide docking score, − 14.06 kcal/mol, and MM-GBSA binding free energy, − 18.08 kcal/mol. The other three lead molecules are also selected along with the top molecule through a critical inspection of their pharmacokinetic properties. HMDB0132640 displayed a better binding affinity than the other three compounds (HMDB0127868, HMDB0134119, and HMDB0125821) due to increased favorable contributions from the intermolecular electrostatic and van der Waals interactions. Further, we have investigated the ligand-induced structural dynamics of the main protease. Overall, we have identified new compounds that can serve as potential leads for developing novel antiviral drugs against SARS-CoV-2 and elucidated molecular mechanisms of their binding to the main protease. GRAPHICAL ABSTRACT: Identification of probable hits from human metabolites against SARS-CoV-2 using integrated computational approaches-Missed against MS [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11030-022-10513-6.
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spelling pubmed-93854162022-08-18 Computational studies indicated the effectiveness of human metabolites against SARS-Cov-2 main protease Roy, Rajarshi Sk, Md Fulbabu Tanwar, Omprakash Kar, Parimal Mol Divers Original Article To fight against the devastating coronavirus disease 2019 (COVID-19), identifying robust anti-SARS-CoV-2 therapeutics from all possible directions is necessary. To contribute to this effort, we selected a human metabolites database containing waters and lipid-soluble metabolites to screen against the 3-chymotrypsin-like proteases (3CL(pro)) protein of SARS-CoV-2. The top 8 hits from virtual screening displayed a docking score varying between ~ − 11 and ~ − 14 kcal/mol. Molecular dynamics simulations complement the virtual screening study in conjunction with the molecular mechanics generalized Born surface area (MM/GBSA) scheme. Our analyses revealed that (HMDB0132640) has the best glide docking score, − 14.06 kcal/mol, and MM-GBSA binding free energy, − 18.08 kcal/mol. The other three lead molecules are also selected along with the top molecule through a critical inspection of their pharmacokinetic properties. HMDB0132640 displayed a better binding affinity than the other three compounds (HMDB0127868, HMDB0134119, and HMDB0125821) due to increased favorable contributions from the intermolecular electrostatic and van der Waals interactions. Further, we have investigated the ligand-induced structural dynamics of the main protease. Overall, we have identified new compounds that can serve as potential leads for developing novel antiviral drugs against SARS-CoV-2 and elucidated molecular mechanisms of their binding to the main protease. GRAPHICAL ABSTRACT: Identification of probable hits from human metabolites against SARS-CoV-2 using integrated computational approaches-Missed against MS [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11030-022-10513-6. Springer International Publishing 2022-08-18 /pmc/articles/PMC9385416/ /pubmed/35978064 http://dx.doi.org/10.1007/s11030-022-10513-6 Text en © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Article
Roy, Rajarshi
Sk, Md Fulbabu
Tanwar, Omprakash
Kar, Parimal
Computational studies indicated the effectiveness of human metabolites against SARS-Cov-2 main protease
title Computational studies indicated the effectiveness of human metabolites against SARS-Cov-2 main protease
title_full Computational studies indicated the effectiveness of human metabolites against SARS-Cov-2 main protease
title_fullStr Computational studies indicated the effectiveness of human metabolites against SARS-Cov-2 main protease
title_full_unstemmed Computational studies indicated the effectiveness of human metabolites against SARS-Cov-2 main protease
title_short Computational studies indicated the effectiveness of human metabolites against SARS-Cov-2 main protease
title_sort computational studies indicated the effectiveness of human metabolites against sars-cov-2 main protease
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385416/
https://www.ncbi.nlm.nih.gov/pubmed/35978064
http://dx.doi.org/10.1007/s11030-022-10513-6
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