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

Significance SARS-CoV-2 has had a crippling impact on human life globally. Vaccine development has been used as a first-line strategy for COVID-19 prevention and mitigation; however, small-molecule drugs are still vitally needed to extend treatment options. Traditional screening methods for identifying biologically active small molecules are sluggish and often sample an insufficient number of compounds to identify suitable hits. Here, we applied a screening method known as DNA-encoded chemistry technology (DEC-Tec) to screen billions of compounds against a critical viral protein, M pro . In rapid fashion, we identified the compound CDD-1713 as a potent and selective M pro inhibitor. This study illuminates DEC-Tec as a highly expeditious strategy toward generating small molecules against critical targets of infectious agents.