Abdelnabi R.Foo C.S.Jochmans D.Vangeel L.De Jonghe S.Augustijns P.Mols R.Weynand B.Wattanakul T.Hoglund R.M.Tarning J.Mowbray C.E.Sjö P.Escudié F.Scandale I.Chatelain E.Neyts J.Mahidol University2023-06-182023-06-182022-12-01Nature Communications Vol.13 No.1 (2022)https://repository.li.mahidol.ac.th/handle/20.500.14594/84142There 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.ChemistryArticleSCOPUS10.1038/s41467-022-28354-02-s2.0-851246796522041172335169114