An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19

  • Science. 2021 Dec 24;374(6575):1586-1593. doi: 10.1126/science.abl4784.
Dafydd R Owen  1 ,  Charlotte M N Allerton  1 ,  Annaliesa S Anderson  2 ,  Lisa Aschenbrenner  3 ,  Melissa Avery  3 ,  Simon Berritt  3 ,  Britton Boras  4 ,  Rhonda D Cardin  2 ,  Anthony Carlo  3 ,  Karen J Coffman  3 ,  Alyssa Dantonio  3 ,  Li Di  3 ,  Heather Eng  3 ,  RoseAnn Ferre  4 ,  Ketan S Gajiwala  4 ,  Scott A Gibson  5 ,  Samantha E Greasley  4 ,  Brett L Hurst  5 ,  Eugene P Kadar  3 ,  Amit S Kalgutkar  1 ,  Jack C Lee  3 ,  Jisun Lee  3 ,  Wei Liu  4 ,  Stephen W Mason  2 ,  Stephen Noell  3 ,  Jonathan J Novak  3 ,  R Scott Obach  3 ,  Kevin Ogilvie  3 ,  Nandini C Patel  1 ,  Martin Pettersson  1 ,  Devendra K Rai  2 ,  Matthew R Reese  3 ,  Matthew F Sammons  1 ,  Jean G Sathish  2 ,  Ravi Shankar P Singh  1 ,  Claire M Steppan  3 ,  Al E Stewart  4 ,  Jamison B Tuttle  1 ,  Lawrence Updyke  1 ,  Patrick R Verhoest  1 ,  Liuqing Wei  3 ,  Qingyi Yang  1 ,  Yuao Zhu  2
Affiliations
  • 1. Pfizer Worldwide Research, Development & Medical, Cambridge, MA 02139, USA.
  • 2. Pfizer Worldwide Research, Development & Medical, Pearl River, NY 10965, USA.
  • 3. Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA.
  • 4. Pfizer Worldwide Research, Development & Medical, La Jolla, CA 92121, USA.
  • 5. Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University; Logan, UT 84322, USA.
PMID: 34726479 DOI: 10.1126/science.abl4784
Abstract

The worldwide outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Alongside vaccines, Antiviral therapeutics are an important part of the healthcare response to countering the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main Protease inhibitor with in vitro pan-human coronavirus Antiviral activity and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro Antiviral cell potency in a phase 1 clinical trial in healthy human participants.

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