Identification of novel and potent inhibitors of SARS-CoV-2 main protease from DNA-encoded chemical libraries.

ABSTRACT: In vitro screening of large compound libraries with automated high-throughput screening is expensive and time-consuming and requires dedicated infrastructures. Conversely, the selection of DNA-encoded chemical libraries (DECLs) can be rapidly performed with routine equipment available in most laboratories. In this study, we identified novel inhibitors of SARS-CoV-2 main protease (M^pro) through the affinity-based selection of the DELopen library (open access for academics), containing 4.2 billion compounds. The identified inhibitors were peptide-like compounds containing an N-terminal electrophilic group able to form a covalent bond with the nucleophilic Cys145 of M^pro, as confirmed by x-ray crystallography. This DECL selection campaign enabled the discovery of

SUBMITTER: Akaberi D 

PROVIDER: S-EPMC11459923 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature