Finding potential inhibitors for Main protease (Mpro) of SARS-CoV-2 through virtual screening and MD simulation studies

SARS-CoV-2 is a highly hazardous species that can infect people with Covid-19 disease, dramatically increasing mortality rates worldwide. Plenty of researches have been done to find drugs or inhibitors, with this study aiming to identify an inhibitor within the ChEMBL database using computational ap...

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Main Authors: N. Anis Ahamed, Ibrahim A. Arif
Format: Article
Language:English
Published: Elsevier 2023-12-01
Series:Saudi Journal of Biological Sciences
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1319562X23002905
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author N. Anis Ahamed
Ibrahim A. Arif
author_facet N. Anis Ahamed
Ibrahim A. Arif
author_sort N. Anis Ahamed
collection DOAJ
description SARS-CoV-2 is a highly hazardous species that can infect people with Covid-19 disease, dramatically increasing mortality rates worldwide. Plenty of researches have been done to find drugs or inhibitors, with this study aiming to identify an inhibitor within the ChEMBL database using computational approaches. From the ChEMBL library, 19,43,048 compounds which are known type of small compounds and proteins were downloaded and docked with the Main protease (Mpro). After performing compound screening using Lipinski’s rule, Qikprop analysis following with virtual Screening, Induced Fit Docking (IFD) and MM-GBSA analysis with the Glide and Prime modules of Schrödinger, the best complex was subjected to MD simulation with Desmond. According to the docking results, small protein 2,371,668 and compound 1,090,395 were docked with Main protease with −12.6, −12.0 kcal/mol dock score and interacted with the functional site residues His 41 and Cys 145, as well as the binding site residues Thr 26, Phe 140, Asn 142, Gly 143, Glu 166, and Gln 189. Complex structures were shown to be steadier by the MD simulation study because both the ligands heavy atoms and the protein Cα atoms' RMSD values fell within acceptable ranges. As a result, this research suggests that the molecule CHEMBL2371668 and the compound CHEMBL1090395 may inhibit the activity of Main protease, and the usefulness of these molecules will be examined further through experimental research.
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spelling doaj.art-fa612f8d349947a5953b6ed3cac4111e2023-12-20T07:33:40ZengElsevierSaudi Journal of Biological Sciences1319-562X2023-12-013012103845Finding potential inhibitors for Main protease (Mpro) of SARS-CoV-2 through virtual screening and MD simulation studiesN. Anis Ahamed0Ibrahim A. Arif1Corresponding author.; Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaSARS-CoV-2 is a highly hazardous species that can infect people with Covid-19 disease, dramatically increasing mortality rates worldwide. Plenty of researches have been done to find drugs or inhibitors, with this study aiming to identify an inhibitor within the ChEMBL database using computational approaches. From the ChEMBL library, 19,43,048 compounds which are known type of small compounds and proteins were downloaded and docked with the Main protease (Mpro). After performing compound screening using Lipinski’s rule, Qikprop analysis following with virtual Screening, Induced Fit Docking (IFD) and MM-GBSA analysis with the Glide and Prime modules of Schrödinger, the best complex was subjected to MD simulation with Desmond. According to the docking results, small protein 2,371,668 and compound 1,090,395 were docked with Main protease with −12.6, −12.0 kcal/mol dock score and interacted with the functional site residues His 41 and Cys 145, as well as the binding site residues Thr 26, Phe 140, Asn 142, Gly 143, Glu 166, and Gln 189. Complex structures were shown to be steadier by the MD simulation study because both the ligands heavy atoms and the protein Cα atoms' RMSD values fell within acceptable ranges. As a result, this research suggests that the molecule CHEMBL2371668 and the compound CHEMBL1090395 may inhibit the activity of Main protease, and the usefulness of these molecules will be examined further through experimental research.http://www.sciencedirect.com/science/article/pii/S1319562X23002905SARS-CoV-2Main protease (Mpro)Covid-19Virtual screeningMD simulation
spellingShingle N. Anis Ahamed
Ibrahim A. Arif
Finding potential inhibitors for Main protease (Mpro) of SARS-CoV-2 through virtual screening and MD simulation studies
Saudi Journal of Biological Sciences
SARS-CoV-2
Main protease (Mpro)
Covid-19
Virtual screening
MD simulation
title Finding potential inhibitors for Main protease (Mpro) of SARS-CoV-2 through virtual screening and MD simulation studies
title_full Finding potential inhibitors for Main protease (Mpro) of SARS-CoV-2 through virtual screening and MD simulation studies
title_fullStr Finding potential inhibitors for Main protease (Mpro) of SARS-CoV-2 through virtual screening and MD simulation studies
title_full_unstemmed Finding potential inhibitors for Main protease (Mpro) of SARS-CoV-2 through virtual screening and MD simulation studies
title_short Finding potential inhibitors for Main protease (Mpro) of SARS-CoV-2 through virtual screening and MD simulation studies
title_sort finding potential inhibitors for main protease mpro of sars cov 2 through virtual screening and md simulation studies
topic SARS-CoV-2
Main protease (Mpro)
Covid-19
Virtual screening
MD simulation
url http://www.sciencedirect.com/science/article/pii/S1319562X23002905
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