Consensus Pharmacophore Strategy For Identifying Novel SARS-Cov-2 M^pro Inhibitors from Large Chemical Libraries.

ABSTRACT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main Protease (M^pro) is an enzyme that cleaves viral polyproteins translated from the viral genome and is critical for viral replication. M^pro is a target for anti-SARS-CoV-2 drug development, and multiple M^pro crystals complexed with competitive inhibitors have been reported. In this study, we aimed to develop an M^pro consensus pharmacophore as a tool to expand the search for inhibitors. We generated a consensus model by aligning and summarizing pharmacophoric points from 152 bioactive conformers of SARS-CoV-2 M^pro inhibitors. Validation against a library of conformers from a subset of ligands showed that our model retrieved poses that reproduced the crystal-binding mode

SUBMITTER: Ruiz-Moreno AJ 

PROVIDER: S-EPMC10966741 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature