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

Abdelnabi, R.; Foo, C. S.-Y.; Jochmans, D.; Vangeel, L.; De Jonghe, S.; Augustijns, P.; Mols, R.; Weynand, B.; Wattanakul, T.; Hoglund, R.; Tarning, J.; Mowbray, C.; Sjo, P.; Escudie, F.; Scandale, I.; Chatelain, E.; Neyts, J.

doi:10.1101/2021.11.04.467077

bioRxiv · 10.1101/2021.11.04.467077

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

Abdelnabi, R.·Foo, C. S.-Y.·Jochmans, D.·Vangeel, L.·De Jonghe, S.·Augustijns, P.·Mols, R.·Weynand, B.·Wattanakul, T.·Hoglund, R.·Tarning, J.·Mowbray, C.·Sjo, P.·Escudie, F.·Scandale, I.·Chatelain, E.·Neyts, J.

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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.

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Abdelnabi, R., Foo, C. S.-Y., Jochmans, D., Vangeel, L., De Jonghe, S., Augustijns, P., Mols, R., Weynand, B., Wattanakul, T., Hoglund, R., Tarning, J., Mowbray, C., Sjo, P., Escudie, F., Scandale, I., Chatelain, E., Neyts, J.. 2021-11-05. The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern. https://doi.org/10.1101/2021.11.04.467077

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