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

The main protease 3CLpro 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 3CLpro. Among these, analogues 31 and 33 emerged as the most interesting candidates with IC 50 values of 95.4 ± 3.1 and 95.0 ± 6.9 µmol L- 1, 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 3CLpro-targeting inhibitors.