Statine-based peptidomimetics as SARS-CoV-2 Papain-like protease inhibitors: in Silico and in vitro studies.

ABSTRACT: We investigated statin-based peptidomimetic compounds as inhibitors of SARS-CoV-2 papain-like protease (PLpro) by in silico methods, including molecular docking/dynamic simulations and ADMET prediction, as well as enzymatic in vitro assays. Five compounds (LQMed 426, 428, 430, 431, and 432) were identified as having promising interactions with the active site and an allosteric site of PLpro. The docking poses in the active site revealed that the compounds interacted with the catalytic triad (Cys111, His272, and Asp286). Compound 426 stood out for forming significant hydrophobic interactions and hydrogen bonds. In molecular dynamic (MD) simulations, there was a tendency for the compounds to migrate to a pocket in the ubiquitin-like (Ubl) domain region, indicating possible allosteric inhibit

SUBMITTER: Pimentel RDP 

PROVIDER: S-EPMC12277432 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature