Nature Communications (Oct 2021)
Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19
- Britton Boras,
- Rhys M. Jones,
- Brandon J. Anson,
- Dan Arenson,
- Lisa Aschenbrenner,
- Malina A. Bakowski,
- Nathan Beutler,
- Joseph Binder,
- Emily Chen,
- Heather Eng,
- Holly Hammond,
- Jennifer Hammond,
- Robert E. Haupt,
- Robert Hoffman,
- Eugene P. Kadar,
- Rob Kania,
- Emi Kimoto,
- Melanie G. Kirkpatrick,
- Lorraine Lanyon,
- Emma K. Lendy,
- Jonathan R. Lillis,
- James Logue,
- Suman A. Luthra,
- Chunlong Ma,
- Stephen W. Mason,
- Marisa E. McGrath,
- Stephen Noell,
- R. Scott Obach,
- Matthew N. O’ Brien,
- Rebecca O’Connor,
- Kevin Ogilvie,
- Dafydd Owen,
- Martin Pettersson,
- Matthew R. Reese,
- Thomas F. Rogers,
- Romel Rosales,
- Michelle I. Rossulek,
- Jean G. Sathish,
- Norimitsu Shirai,
- Claire Steppan,
- Martyn Ticehurst,
- Lawrence W. Updyke,
- Stuart Weston,
- Yuao Zhu,
- Kris M. White,
- Adolfo García-Sastre,
- Jun Wang,
- Arnab K. Chatterjee,
- Andrew D. Mesecar,
- Matthew B. Frieman,
- Annaliesa S. Anderson,
- Charlotte Allerton
Affiliations
- Britton Boras
- Worldwide Research and Development, Pfizer Inc
- Rhys M. Jones
- Worldwide Research and Development, Pfizer Inc
- Brandon J. Anson
- Department of Biological Sciences, Purdue University
- Dan Arenson
- Worldwide Research and Development, Pfizer Inc
- Lisa Aschenbrenner
- Worldwide Research and Development, Pfizer Inc
- Malina A. Bakowski
- Calibr, a division of The Scripps Research Institute
- Nathan Beutler
- Department of Immunology and Microbiology, The Scripps Research Institute
- Joseph Binder
- Worldwide Research and Development, Pfizer Inc
- Emily Chen
- Calibr, a division of The Scripps Research Institute
- Heather Eng
- Worldwide Research and Development, Pfizer Inc
- Holly Hammond
- Department of Microbiology and Immunology University of Maryland School of Medicine
- Jennifer Hammond
- Worldwide Research and Development, Pfizer Inc.
- Robert E. Haupt
- Department of Microbiology and Immunology University of Maryland School of Medicine
- Robert Hoffman
- Worldwide Research and Development, Pfizer Inc
- Eugene P. Kadar
- Worldwide Research and Development, Pfizer Inc
- Rob Kania
- Worldwide Research and Development, Pfizer Inc
- Emi Kimoto
- Worldwide Research and Development, Pfizer Inc
- Melanie G. Kirkpatrick
- Calibr, a division of The Scripps Research Institute
- Lorraine Lanyon
- Worldwide Research and Development, Pfizer Inc
- Emma K. Lendy
- Department of Biochemistry, Purdue University
- Jonathan R. Lillis
- Worldwide Research and Development, Pfizer Inc
- James Logue
- Department of Microbiology and Immunology University of Maryland School of Medicine
- Suman A. Luthra
- Worldwide Research and Development, Pfizer Inc
- Chunlong Ma
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona
- Stephen W. Mason
- Worldwide Research and Development, Pfizer Inc
- Marisa E. McGrath
- Department of Microbiology and Immunology University of Maryland School of Medicine
- Stephen Noell
- Worldwide Research and Development, Pfizer Inc
- R. Scott Obach
- Worldwide Research and Development, Pfizer Inc
- Matthew N. O’ Brien
- Worldwide Research and Development, Pfizer Inc
- Rebecca O’Connor
- Worldwide Research and Development, Pfizer Inc
- Kevin Ogilvie
- Worldwide Research and Development, Pfizer Inc
- Dafydd Owen
- Worldwide Research and Development, Pfizer Inc
- Martin Pettersson
- Worldwide Research and Development, Pfizer Inc
- Matthew R. Reese
- Worldwide Research and Development, Pfizer Inc
- Thomas F. Rogers
- Department of Immunology and Microbiology, The Scripps Research Institute
- Romel Rosales
- Department of Microbiology, Icahn School of Medicine at Mount Sinai
- Michelle I. Rossulek
- Worldwide Research and Development, Pfizer Inc
- Jean G. Sathish
- Worldwide Research and Development, Pfizer Inc.
- Norimitsu Shirai
- Worldwide Research and Development, Pfizer Inc
- Claire Steppan
- Worldwide Research and Development, Pfizer Inc
- Martyn Ticehurst
- Worldwide Research and Development, Pfizer Inc
- Lawrence W. Updyke
- Worldwide Research and Development, Pfizer Inc
- Stuart Weston
- Department of Microbiology and Immunology University of Maryland School of Medicine
- Yuao Zhu
- Worldwide Research and Development, Pfizer Inc.
- Kris M. White
- Department of Microbiology, Icahn School of Medicine at Mount Sinai
- Adolfo García-Sastre
- Department of Microbiology, Icahn School of Medicine at Mount Sinai
- Jun Wang
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona
- Arnab K. Chatterjee
- Calibr, a division of The Scripps Research Institute
- Andrew D. Mesecar
- Department of Biological Sciences, Purdue University
- Matthew B. Frieman
- Department of Microbiology and Immunology University of Maryland School of Medicine
- Annaliesa S. Anderson
- Worldwide Research and Development, Pfizer Inc.
- Charlotte Allerton
- Worldwide Research and Development, Pfizer Inc
- DOI
- https://doi.org/10.1038/s41467-021-26239-2
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 17
Abstract
The 3CL protease of SARS-CoV-2 is inhibited by PF-00835231 in vitro. Here, the authors show that the prodrug PF-07304814 has broad spectrum activity, inhibiting SARS-CoV and SARS-CoV-2 in mice and its ADME and safety profile support clinical development.
