Identification of catechin as main protease inhibitor of SARS-CoV-2 Omicron variant using molecular docking, molecular dynamics, PCA, DCCM, MM/GBSA and ADMET profiling.

Abstract

The Omicron variant of SARS-CoV-2 spreads more rapidly than other variants and can affect even vaccinated individuals. The Omicron variant main protease (Mpro), crucial for viral replication and transcription, is an attractive target for antiviral drug discovery. This research aims to investigate non-toxic flavonoids that follow Lipinski's rule of five (RO5) and inhibit the Omicron variant Mpro. Molecular docking was performed on 35 flavonoids screened by analysing their medicinal values and adherence to RO5. Catechin (2-(3,4-dihydroxyphenol) chroman-3,5,7-triol), a non-toxic natural compound having predicted toxicity class 6 and LD50 value 10,000 mg/kg, exhibited a docking score of -7.1 kcal/mol with Mpro. The Mpro-catechin complex remained stable during 250 ns MD simulations. The post-MD free energy (MM/GBSA) calculations showed a binding energy of -20.5 kcal/mol, indicating strong interactions with the active amino acid residues. These findings suggest that catechin is a promising drug candidate against the Omicron variant.