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

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

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 act...

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Bibliographic Details
Main Authors: Abdelnabi, R, Foo, CS, Jochmans, D, Vangeel, L, De Jonghe, S, Augustijns, P, Mols, R, Weynand, B, Wattanakul, T, Hoglund, RM, Tarning, J, Mowbray, CE, Sjö, P, Escudié, F, Scandale, I, Chatelain, E, Neyts, J
Format: Journal article
Language:English
Published: Springer Nature 2022
Description
Summary: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.

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