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 acti...

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Detalles Bibliográficos
Autores principales: Abdelnabi, Rana, Foo, Caroline S., Jochmans, Dirk, Vangeel, Laura, De Jonghe, Steven, Augustijns, Patrick, Mols, Raf, Weynand, Birgit, Wattanakul, Thanaporn, Hoglund, Richard M., Tarning, Joel, Mowbray, Charles E., Sjö, Peter, Escudié, Fanny, Scandale, Ivan, Chatelain, Eric, Neyts, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847371/
https://www.ncbi.nlm.nih.gov/pubmed/35169114
http://dx.doi.org/10.1038/s41467-022-28354-0
Descripción
Sumario: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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