Molecular Recognition of SARS-CoV-2 Mpro Inhibitors: Insights from Cheminformatics and Quantum Chemistry.

ABSTRACT: The SARS-CoV-2 main protease (Mpro), essential for viral replication, remains a prime target for antiviral drug design against COVID-19 and related coronaviruses. In this study, we present a systematic investigation into the molecular determinants of Mpro inhibition using an integrated approach combining large-scale data mining, cheminformatics, and quantum chemical calculations. A curated dataset comprising 963 high-resolution structures of Mpro-ligand complexes-348 covalent and 615 non-covalent inhibitors-was mined from the Protein Data Bank. Cheminformatics analysis revealed distinct physicochemical profiles for each inhibitor class: covalent inhibitors tend to exhibit higher hydrogen bonding capacity and sp³ character, while non-covalent inhibitors are enriched in aromatic r

SUBMITTER: Olosunde A 

PROVIDER: S-EPMC12114402 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature