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An Oral SARS-CoV-2 Mpro Inhibitor Clinical Candidate for the Treatment of COVID-19
Dafydd R Owen; Charlotte M N Allerton; Annaliesa S Anderson; Lisa Aschenbrenner; Melissa Avery; Simon Berritt; Britton Boras; Rhonda D Cardin; Anthony Carlo; Karen Coffman; Alyssa Dantonio; Li Di; Heather Eng; RoseAnn Ferre; Ketan S Gajiwala; Scott A Gibson; Samantha E Greasley; Brett L Hurst; Eugene P Kadar; Amit S Kalgutkar; Jack C Lee; Jisun Lee; Wei Liu; Stephen W Mason; Stephen Noell; Jonathan J Novak; R Scott Obach; Kevin Ogilvie; Nandini C Patel; Martin Pettersson; Devendra K Rai; Matthew R Reese; Matthew F Sammons; Jean G Sathish; Ravi Shankar P Singh; Claire M Steppan; Al E Stewart; Jamison B Tuttle; Lawrence Updyke; Patrick R Verhoest; Liuqing Wei; Qingyi Yang; Yuao Zhu.
Afiliação
  • Dafydd R Owen; Pfizer Worldwide Research, Development & Medical; Cambridge, MA 02139, USA
  • Charlotte M N Allerton; Pfizer Worldwide Research, Development & Medical; Cambridge, MA 02139, USA
  • Annaliesa S Anderson; Pfizer Worldwide Research, Development & Medical; Pearl River, NY 10965, USA
  • Lisa Aschenbrenner; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Melissa Avery; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Simon Berritt; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Britton Boras; Pfizer Worldwide Research, Development & Medical; La Jolla, CA 92121, USA
  • Rhonda D Cardin; Pfizer Worldwide Research, Development & Medical; Pearl River, NY 10965, USA
  • Anthony Carlo; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Karen Coffman; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Alyssa Dantonio; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Li Di; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Heather Eng; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • RoseAnn Ferre; Pfizer Worldwide Research, Development & Medical; La Jolla, CA 92121, USA
  • Ketan S Gajiwala; Pfizer Worldwide Research, Development & Medical; La Jolla, CA 92121, USA
  • Scott A Gibson; Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University; Logan, UT 84322, USA
  • Samantha E Greasley; Pfizer Worldwide Research, Development & Medical; La Jolla, CA 92121, USA
  • Brett L Hurst; Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University; Logan, UT 84322, USA
  • Eugene P Kadar; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Amit S Kalgutkar; Pfizer Worldwide Research, Development & Medical; Cambridge, MA 02139, USA
  • Jack C Lee; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Jisun Lee; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Wei Liu; Pfizer Worldwide Research, Development & Medical; La Jolla, CA 92121, USA
  • Stephen W Mason; Pfizer Worldwide Research, Development & Medical; Pearl River, NY 10965, USA
  • Stephen Noell; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Jonathan J Novak; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • R Scott Obach; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Kevin Ogilvie; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Nandini C Patel; Pfizer Worldwide Research, Development & Medical; Cambridge, MA 02139, USA
  • Martin Pettersson; Pfizer Worldwide Research, Development & Medical; Cambridge, MA 02139, USA
  • Devendra K Rai; Pfizer Worldwide Research, Development & Medical; Pearl River, NY 10965, USA
  • Matthew R Reese; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Matthew F Sammons; Pfizer Worldwide Research, Development & Medical; Cambridge, MA 02139, USA
  • Jean G Sathish; Pfizer Worldwide Research, Development & Medical; Pearl River, NY 10965, USA
  • Ravi Shankar P Singh; Pfizer Worldwide Research, Development & Medical; Cambridge, MA 02139, USA
  • Claire M Steppan; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Al E Stewart; Pfizer Worldwide Research, Development & Medical; La Jolla, CA 92121, USA
  • Jamison B Tuttle; Pfizer Worldwide Research, Development & Medical; Cambridge, MA 02139, USA
  • Lawrence Updyke; Pfizer Worldwide Research, Development & Medical; Cambridge, MA 02139, USA
  • Patrick R Verhoest; Pfizer Worldwide Research, Development & Medical; Cambridge, MA 02139, USA
  • Liuqing Wei; Pfizer Worldwide Research, Development & Medical; Groton, CT 06340, USA
  • Qingyi Yang; Pfizer Worldwide Research, Development & Medical; Cambridge, MA 02139, USA
  • Yuao Zhu; Pfizer Worldwide Research, Development & Medical; Pearl River, NY 10965, USA
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21261232
ABSTRACT
AbstractThe worldwide outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become an established global pandemic. Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to counter 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 I clinical trial in healthy human participants. ClinicalTrials.gov Identifier NCT04756531 One-Sentence SummaryPF-07321332 is disclosed as a novel, orally active, investigational small-molecule inhibitor of the SARS-CoV-2 main protease, which is being evaluated in clinical trials for the treatment of COVID-19.
Licença
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Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Tipo de estudo: Experimental_studies / Estudo prognóstico / Rct Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Preprint
Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Tipo de estudo: Experimental_studies / Estudo prognóstico / Rct Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Preprint
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