The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern
Rana Abdelnabi, Caroline S. Foo, Dirk Jochmans, Laura Vangeel, Steven De Jonghe, Patrick Augustijns, Raf Mols, Birgit Weynand, Thanaporn Wattanakul, Richard M. Hoglund, Joel Tärning, Charles E. Mowbray, Peter Sjö, Fanny Escudié, Ivan Scandale, Eric Chatelain, Johan Neyts
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.