Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19.

ABSTRACT: The RNA-dependent RNA polymerase (RdRp), 3C-like protease (3CL^pro), and papain-like protease (PL^pro) are pivotal components in the viral life cycle of SARS-CoV-2, presenting as promising therapeutic targets. Currently, all FDA-approved antiviral drugs against SARS-CoV-2 are RdRp or 3CL^pro inhibitors. However, the mutations causing drug resistance have been observed in RdRp and 3CL^pro from SARS-CoV-2, which makes it necessary to develop antivirals with novel mechanisms. Through the application of a structure-based drug design (SBDD) approach, we discover a series of novel potent non-covalent PL^pro inhibitors with remarkable in vitro potency and in vivo PK properties. The co-crystal structures of PL^pro with lead compounds reve

SUBMITTER: Lu Y 

PROVIDER: S-EPMC11585628 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature