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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.

Original publication




Journal article


Nat Commun

Publication Date





A549 Cells, Administration, Oral, Animals, COVID-19, Chlorocebus aethiops, Coronavirus 3C Proteases, Cricetinae, Disease Models, Animal, Humans, Lactams, Leucine, Mesocricetus, Nitriles, Proline, Respiratory Mucosa, SARS-CoV-2, Vero Cells, Viral Protease Inhibitors, Virus Replication