PF-07817883 (Ibuzatrelvir): A Second-Generation SARS-CoV-2 Main Protease Inhibitor with Improved Metabolic Stability
PF-07817883 (ibuzatrelvir) is an oral, second-generation SARS-CoV-2 Mpro inhibitor developed by Pfizer. These efforts follow the success of Pfizer's antiviral combination drug, Paxlovid, which was granted Emergency Use Authorization by the FDA for the treatment of COVID-19 just 17 months after its first synthesis in July 2020. PF-07817883 was granted Fast Track designation and recently completed a Ph. II clinical trial to evaluate its safety and efficacy in outpatient adults with COVID-19 symptoms. This article details the discovery strategy for PF-07817883, which includes addressing metabolic soft spots identified through MetID studies, recent clinical developments, and more.