Computational Investigation on the Efficiency of Small Molecule Inhibitors Identified from Indian Spices against SARS-CoV-2 Mpro
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Published:2022-06-06
Issue:3
Volume:13
Page:235
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ISSN:2069-5837
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Container-title:Biointerface Research in Applied Chemistry
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language:en
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Short-container-title:Biointerface Res Appl Chem
Abstract
Recently, small compounds from Indian spices (Carnosol, Arjunglucoside-I, and Rosmanol) have been identified as SARS-CoV-2 main protease (Mpro) inhibitors. The structural dynamics and characteristic features of binding of these small molecules to the SARS-CoV-2 Mpro are not well understood. Here, we have constructed the potential of mean force (PMF) for dissociating Mpro-small molecule inhibitor complexes from the umbrella sampling simulations using the weighted histogram analysis method. Mpro-small molecule inhibitor complexes exhibited relatively higher dissociation energy values than the alpha-ketoamide-Mpro complex (positive control) from the PMF calculations. We found that binding affinity between protein and ligand is higher in Mpro-Arjunglucoside-I complex [∆Gbind = -19.74 kcal mol-1 from MM-GBSA and ∆Gbind = -9.13 kcal mol-1 from MM-PBSA] than in other three SARS-CoV-2 small molecule complexes. The MM-GBSA/MM-PBSA calculations revealed that the small molecule inhibitors studied in this work have substantially higher binding affinity for Mpro. We found the residues present in SARS-CoV-2 Mpro's binding pocket contributed the most binding free energy to SARS-CoV-2 Mpro-small molecule interactions. Our findings emphasize the structural and binding features of the identified small molecule inhibitors with SARS-CoV-2 Mpro, which could be relevant in developing therapeutic candidates to combat SARS-CoV-2.
Publisher
AMG Transcend Association
Subject
Molecular Biology,Molecular Medicine,Biochemistry,Biotechnology
Cited by
1 articles.
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