Discovery of a Novel Inhibitor of Coronavirus 3CL Protease for the Potential Treatment of COVID-19-Reference-Cited by-同舟云学术

Discovery of a Novel Inhibitor of Coronavirus 3CL Protease for the Potential Treatment of COVID-19

Published:2020-09-13 Issue: Volume: Page:
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Author:

Boras Britton^ORCID,Jones Rhys M.^ORCID,Anson Brandon J.^ORCID,Arenson Dan,Aschenbrenner Lisa,Bakowski Malina A.^ORCID,Beutler Nathan^ORCID,Binder Joseph,Chen Emily,Eng Heather^ORCID,Hammond Holly,Hammond Jennifer,Haupt Robert E.,Hoffman Robert^ORCID,Kadar Eugene P.,Kania Rob,Kimoto Emi^ORCID,Kirkpatrick Melanie G.,Lanyon Lorraine,Lendy Emma K.^ORCID,Lillis Jonathan R.,Logue James,Luthra Suman A.,Ma Chunlong^ORCID,Mason Stephen W.,McGrath Marisa E.,Noell Stephen,Obach R. Scott^ORCID,O’Brien Matthew N.^ORCID,O’Connor Rebecca,Ogilvie Kevin,Owen Dafydd^ORCID,Pettersson Martin,Reese Matthew R,Rogers Thomas F.,Rossulek Michelle I.,Sathish Jean G.,Shirai Norimitsu,Steppan Claire^ORCID,Ticehurst Martyn,Updyke Lawrence W.,Weston Stuart,Zhu Yuao,Wang Jun^ORCID,Chatterjee Arnab K.^ORCID,Mesecar Andrew D.^ORCID,Frieman Matthew B.,Anderson Annaliesa S.^ORCID,Allerton Charlotte

Abstract

AbstractCOVID-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.

Publisher

Cold Spring Harbor Laboratory

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