DNA-encoded chemical libraries yield non-covalent and non-peptidic SARS-CoV-2 main protease inhibitors.

ABSTRACT: The development of SARS-CoV-2 main protease (M^pro) inhibitors for the treatment of COVID-19 has mostly benefitted from X-ray structures and preexisting knowledge of inhibitors; however, an efficient method to generate M^pro inhibitors, which circumvents such information would be advantageous. As an alternative approach, we show here that DNA-encoded chemistry technology (DEC-Tec) can be used to discover inhibitors of M^pro. An affinity selection of a 4-billion-membered DNA-encoded chemical library (DECL) using M^pro as bait produces novel non-covalent and non-peptide-based small molecule inhibitors of M^pro with low nanomolar K_i values. Furthermore, these compounds demonstrate efficacy against mutant forms of M^pro tha

SUBMITTER: Jimmidi R 

PROVIDER: S-EPMC10403511 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature