PT  - JOURNAL ARTICLE
AU  - Britton Boras
AU  - Rhys M. Jones
AU  - Brandon J. Anson
AU  - Dan Arenson
AU  - Lisa Aschenbrenner
AU  - Malina A. Bakowski
AU  - Nathan Beutler
AU  - Joseph Binder
AU  - Emily Chen
AU  - Heather Eng
AU  - Jennifer Hammond
AU  - Robert Hoffman
AU  - Eugene P. Kadar
AU  - Rob Kania
AU  - Emi Kimoto
AU  - Melanie G. Kirkpatrick
AU  - Lorraine Lanyon
AU  - Emma K. Lendy
AU  - Jonathan R. Lillis
AU  - Suman A. Luthra
AU  - Chunlong Ma
AU  - Stephen Noell
AU  - R. Scott Obach
AU  - Matthew N. O’ Brien
AU  - Rebecca O’Connor
AU  - Kevin Ogilvie
AU  - Dafydd Owen
AU  - Martin Pettersson
AU  - Matthew R Reese
AU  - Thomas F. Rogers
AU  - Michelle I. Rossulek
AU  - Jean G. Sathish
AU  - Claire Steppan
AU  - Martyn Ticehurst
AU  - Lawrence W. Updyke
AU  - Yuao Zhu
AU  - Jun Wang
AU  - Arnab K. Chatterjee
AU  - Andrew D. Mesecar
AU  - Annaliesa S. Anderson
AU  - Charlotte Allerton
TI  - Discovery of a Novel Inhibitor of Coronavirus 3CL Protease as a Clinical Candidate for the Potential Treatment of COVID-19
AID  - 10.1101/2020.09.12.293498
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.12.293498
4099  - http://biorxiv.org/content/early/2020/09/13/2020.09.12.293498.short
4100  - http://biorxiv.org/content/early/2020/09/13/2020.09.12.293498.full
AB  - COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential to the viral life cycle 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, and in vitro antiviral activity data to warrant clinical evaluation.One Sentence Summary The phosphate prodrug PF-07304814 is disclosed as an investigational novel intravenous small molecule 3CL protease inhibitor for COVID-19.Competing Interest StatementA.D.M has a sponsored program contract with Pfizer to test compounds for inhibition of coronavirus proteases. JW has a sponsored research agreement with Pfizer to test compounds for inhibition of coronavirus proteases.