Discovery of SARS-CoV-2 Papain-like Protease Inhibitors

SARS-CoV-2 antivirals which have been clinically approved or are in late-stage development are directed against either the RNA-dependent RNA polymerase (RdRp) or the main protease (Mpro). With the possibility of resistance developing over time, there is a need for additional oral antivirals directed against currently undrugged viral targets.

Conserved across coronaviruses, the SARS-CoV-2 papain-like protease (PLpro), along with Mpro, is responsible for polyprotein processing, which is required for the generation of a functional viral replicase. WuXi AppTec scientists recently contributed to a study on the discovery of potent, selective, and orally bioavailable SARS-CoV-2 PLpro inhibitors with robust efficacy in a mouse-adapted model of COVID-19 infection.