Factual insights of the allosteric inhibition mechanism of SARS-CoV-2 main protease by quercetin: an in silico analysis
Abstract
SARS-CoV-2 main protease (M pro ) cleaves the viral polypeptide 1a and 1ab in a site-specific ((L-Q|(S, A, G)) manner and produce functional enzymes for mediating viral replication. Numerous studies have reported synthetic competitive inhibitors against this target enzyme but increase in substrate concentration often reduces the effectiveness of such inhibitors. Allosteric inhibition by natural compound can provide safe and effective treatment by alleviating this limitation. Present study deals with in silico allosteric inhibition analysis of quercetin, against SARS-CoV-2-M pro . Molecular docking of quercetin with M pro revealed consistent binding of quercetin at a site other than active site in multiple runs, with the highest binding energy of − 8.31 kcal/mol, forming 6 H-bonds with residues Gln127, Cys128, Lys137, Asp289 and Glu290. Molecular dynamic simulation of 50 ns revealed high stability of M pro -quercetin complex with RMSD values ranging from 0.1 to 0.25 nm. Moreover, native-M pro and M pro -quercetin complex conformations extracted at different time points from simulation trajectories were subjected to active site-specific docking with modelled substrate peptide (AVLQSGFR) by ZDOCK server. Results displayed site-specific cleavage of peptide when docked with native-M pro . While substrate peptide remained intact when docked with M pro -quercetin complex, also the binding energy of peptide reduced from 785 to 86 from 1 to 50 ns as quercetin induced alterations in…
Read the paper
Related studies
- Quercetin Influences Quorum Sensing in Food Borne Bacteria: In-Vitro and In-Silico Evidence
- Phenolic-protein interactions: insight from in-silico analyses – a review
- In Silico Discovery of Candidate Drugs against Covid-19
- Neuropharmacological Effects of Quercetin: A Literature-Based Review
- In vitro and in silico anti-dengue activity of compounds obtained from Psidium guajava through bioprospecting
- Effect of Quercetin Rich Onion Extracts on Bacterial Quorum Sensing
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.