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This article discusses the identification and development of a series of SARS-CoV-2 main protease (MPro) inhibitors, focusing on the effects of ortho-substitution within the P3 biphenyl group. The study reveals that incorporating an ortho substituent enhances binding and potency, although selectivity against off-target cysteine proteases remains suboptimal. Further modifications led to the discovery of compound 22e, which exhibits high potency and cellular activity as an MPro inhibitor.

Author

Robert McCuaig

Language

EN