SARS-CoV-2 is the etiological agent responsible for the global COVID-19 outbreak. The main protease (M pro ) of SARS-CoV-2 is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds ( 11a and 11b ) targeting M pro . Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The X-ray crystal structures of SARS-CoV-2 M pro in complex with 11a or 11b , both determined at 1.5 Å resolution, showed that the aldehyde groups of 11a and 11b are covalently bound to Cys145 of M pro . Both compounds showed good PK properties in vivo, and 11a also exhibited low toxicity, suggesting that these compounds are promising drug candidates.
【초록키워드】 SARS-CoV-2, Transcription, Infection, Toxicity, protease, anti-SARS-CoV-2, X-ray, COVID-19 outbreak, viral replication, crystal structure, group, in vivo, drug candidates, enzyme, complex, Compound, M pro, etiological agent, inhibitory activity, Cys145, responsible, exhibited, these compound, 【제목키워드】 protease, antiviral drug, candidate, the SARS-CoV-2,