Diastereomeric Resolution Yields Highly Potent Inhibitor of SARS-CoV-2 Main Protease.

ABSTRACT: SARS-CoV-2 is the causative agent behind the COVID-19 pandemic. The main protease (M^pro, 3CL^pro) of SARS-CoV-2 is a key enzyme that processes polyproteins translated from the viral RNA. M^pro is therefore an attractive target for the design of inhibitors that block viral replication. We report the diastereomeric resolution of the previously designed SARS-CoV-2 M^pro α-ketoamide inhibitor 13b. The pure (S,S,S)-diastereomer, 13b-K, displays an IC₅₀ of 120 nM against the M^pro and EC₅₀ values of 0.8-3.4 μM for antiviral activity in different cell types. Crystal structures have been elucidated for the M^pro complexes with each of the major diastereomers, the active (S,S,S)-13b (13

SUBMITTER: Cooper MS 

PROVIDER: S-EPMC9574927 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature