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 Tarning, Charles E Mowbray, Peter Sjö, Fanny Escudié, Ivan Scandale, Eric Chatelain, Johan Neyts
doi:10.1101/2021.11.04.467077
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.
Ethics Housing conditions and experimental procedures were done with the approval and under the guidelines of the ethics committee of animal experimentation of KU Leuven (license P065-2020).
Conflict of interest
None to declare
Author
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