Discovery of SARS-CoV-2 papain-like protease inhibitors through a combination of high-throughput screening and FlipGFP-based reporter assay.

ABSTRACT: The papain-like protease (PL ^pro ) of SARS-CoV-2 is a validated antiviral drug target. PL ^pro is involved in the cleavage of viral polyproteins and antagonizing host innate immune response through its deubiquitinating and deISG15ylating activities, rendering it a high profile antiviral drug target. Through a FRET-based high-throughput screening, several hits were identified as PL ^pro inhibitors with IC ₅₀ values at the single-digit micromolar range. Subsequent lead optimization led to potent inhibitors with IC ₅₀ values ranging from 0.56 to 0.90 µM. To help prioritize lead compounds for the cellular antiviral assay against SARS-CoV-2, we developed the cell-based FlipGFP assay that is suitable for quantifying the intracellular enzymatic

SUBMITTER: Xia Z 

PROVIDER: S-EPMC7987026 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature