In silico screening-based discovery of novel covalent inhibitors of the SARS-CoV-2 3CL protease.

ABSTRACT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL protease (3CL^pro) has been regarded as an extremely promising antiviral target for the treatment of coronavirus disease 2019 (COVID-19). Here, we carried out a virtual screening based on commercial compounds database to find novel covalent non-peptidomimetic inhibitors of this protease. It allowed us to identify 3 hit compounds with potential covalent binding modes, which were evaluated through an enzymatic activity assay of the SARS-CoV-2 3CL^pro. Moreover, an X-ray crystal structure of the SARS-CoV-2 3CL^pro in complex with compound 8, the most potent hit with an IC₅₀ value of 8.50 μM, confirmed the covalent binding of the predicted warhead to the catalytic residue C145, as well

SUBMITTER: Xiong M 

PROVIDER: S-EPMC8783839 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature