The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern

Nat Commun. 2022 Feb 15;13(1):719. doi: 10.1038/s41467-022-28354-0.

Abstract

There is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-07321332 (PF-332), a potent inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed orally and that is in clinical development. We here report that PF-332 exerts equipotent in vitro activity against the four SARS-CoV-2 variants of concerns (VoC) and that it can completely arrest replication of the alpha variant in primary human airway epithelial cells grown at the air-liquid interface. Treatment of Syrian Golden hamsters with PF-332 (250 mg/kg, twice daily) completely protected the animals against intranasal infection with the beta (B.1.351) and delta (B.1.617.2) SARS-CoV-2 variants. Moreover, treatment of SARS-CoV-2 (B.1.617.2) infected animals with PF-332 completely prevented transmission to untreated co-housed sentinels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Administration, Oral
  • Animals
  • COVID-19 / prevention & control
  • COVID-19 / transmission
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Chlorocebus aethiops
  • Coronavirus 3C Proteases / antagonists & inhibitors
  • Cricetinae
  • Disease Models, Animal*
  • Humans
  • Lactams / administration & dosage*
  • Lactams / pharmacokinetics
  • Leucine / administration & dosage*
  • Leucine / pharmacokinetics
  • Mesocricetus
  • Nitriles / administration & dosage*
  • Nitriles / pharmacokinetics
  • Proline / administration & dosage*
  • Proline / pharmacokinetics
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / virology
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / enzymology
  • SARS-CoV-2 / physiology
  • Vero Cells
  • Viral Protease Inhibitors / administration & dosage*
  • Viral Protease Inhibitors / pharmacokinetics
  • Virus Replication / drug effects

Substances

  • Lactams
  • Nitriles
  • Viral Protease Inhibitors
  • nirmatrelvir
  • Proline
  • 3C-like proteinase, SARS-CoV-2
  • Coronavirus 3C Proteases
  • Leucine

Supplementary concepts

  • SARS-CoV-2 variants