DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 M^pro inhibitors.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration-approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (M^pro) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition constant [K_i] = 20 nM). CDD-1713, a smal

SUBMITTER: Chamakuri S 

PROVIDER: S-EPMC8433497 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature