作者
Britton Boras,Rhys M. Jones,Brandon J. Anson,Dan Arenson,Lisa Aschenbrenner,Malina A. Bakowski,Nathan Beutler,Joseph John Binder,Emily I. Chen,Heather Eng,Holly L. Hammond,Jennifer Hammond,Rob Haupt,Robert M. Hoffman,Eugene P. Kadar,Robert Steven Kania,Emi Kimoto,Melanie G. Kirkpatrick,Lorraine F. Lanyon,Emma K. Lendy,Lillis,James Logue,Suman Luthra,Chuang Ma,Stephen W. Mason,Marisa McGrath,Stephen Noell,Obach Rs,O’Brien Mn,Rebecca E. O’Connor,Kevin Ogilvie,Dafydd R. Owen,Martin Pettersson,Reese Mr,Thomas F. Rogers,Michelle Rossulek,Jean G. Sathish,Norimitsu Shirai,Claire M. Steppan,Martyn D. Ticehurst,Lawrence W. Updyke,Stuart Weston,Yuao Zhu,Jun Wang,Abhishek Chatterjee,Andrew D. Mesecar,Matthew B. Frieman,Annaliesa S. Anderson,Charlotte Moira Norfor Allerton
摘要
Abstract COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. The designed phosphate prodrug PF-07304814 is metabolized to PF-00835321 which is a potent inhibitor in vitro of the coronavirus family 3CL pro, with selectivity over human host protease targets. Furthermore, PF-00835231 exhibits potent in vitro antiviral activity against SARS-CoV-2 as a single agent and it is additive/synergistic in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of this compound as a potential COVID-19 treatment.