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Exploring potential SARS-CoV-2 Mpro non-covalent inhibitors through docking, pharmacophore profile matching, molecular dynamic simulation, and MM-GBSA.

Authors :
Shi Y
Dong L
Ju Z
Li Q
Cui Y
Liu Y
He J
Ding X
Source :
Journal of molecular modeling [J Mol Model] 2023 Apr 13; Vol. 29 (5), pp. 138. Date of Electronic Publication: 2023 Apr 13.
Publication Year :
2023

Abstract

Context: In the replication of SARS-CoV-2, the main protease (Mpro/3CLpro) is significant. It is conserved in a number of novel coronavirus variations, and no known human proteases share its cleavage sites. Therefore, 3CLpro is an ideal target. In the report, we screened five potential inhibitors (1543, 2308, 3717, 5606, and 9000) of SARS-CoV-2 Mpro through a workflow. The calculation of MM-GBSA binding free energy showed that three of the five potential inhibitors (1543, 2308, 5606) had similar inhibitor effects to X77 against Mpro of SARS-CoV-2. In conclusion, the manuscript lays the groundwork for the design of Mpro inhibitors.<br />Methods: In the virtual screening phase, we used structure-based virtual screening (Qvina2.1) and ligand-based virtual screening (AncPhore). In the molecular dynamic simulation part, we used the Amber14SB + GAFF force field to perform molecular dynamic simulation of the complex for 100 ns (Gromacs2021.5) and performed MM-GBSA binding free energy calculation according to the simulation trajectory.<br /> (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Details

Language :
English
ISSN :
0948-5023
Volume :
29
Issue :
5
Database :
MEDLINE
Journal :
Journal of molecular modeling
Publication Type :
Academic Journal
Accession number :
37055578
Full Text :
https://doi.org/10.1007/s00894-023-05534-3