α-Heteroarylthiomethyl ketones: Small molecule inhibitors of 3CL.

Publication date: Jun 01, 2025

The main protease 3CL of the SARS-CoV-2 virus is a well–established therapeutic target for the treatment of COVID-19. In this study, we screened an in-house compound library and identified a series of α-heteroarylthiomethyl ketones as inhibitors of 3CL. Among these, analogues 31 and 33 emerged as the most interesting candidates with IC values of 95. 4 +/- 3. 1 and 95. 0 +/- 6. 9 umol L , respectively. Preliminary in vitro studies suggest a potential covalent mode of inhibition, although further studies are required to confirm this mechanism. These findings provide a new chemical scaffold for the development of 3CL-targeting inhibitors.

Semantics

Original Article