A #clinical #SARS-CoV-2 #Mpro #inhibitor blocks replication of multiple #enteroviruses and confers oral in vivo protection in animal models
Abstract Enteroviruses, which belong to the family Picornaviridae, cause hand, foot, and mouth disease (HFMD), respiratory symptoms, and severe neurological complications in children . Since vaccines cannot provide cross-protection against different serotypes of enteroviruses , the development of broad-spectrum anti-enteroviral drugs is imperative . The viral 3C protease (3Cpro), which is essential for polyprotein processing represents a validated target for therapeutic intervention . Importantly, enterovirus 3Cpro shares conserved structural and catalytic features with coronavirus main protease (Mpro, also known as 3C-like protease, 3CLpro), providing a rationale for cross-target inhibitor repurposing . Through targeted screening of peptidomimetic protease inhibitors, a clinical-stage SARS-CoV-2 Mpro inhibitor was identified as a potent inhibitor of enterovirus A71 (EV71) 3Cpro. Bofutrelvir displayed nanomolar antiviral activity in multiple cell lines and demonstrated broad-spec...