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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.

Original publication

DOI

10.1038/s41467-022-28354-0

Type

Journal article

Journal

Nature communications

Publication Date

15/02/2022

Volume

13

Addresses

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, 3000, Leuven, Belgium.

Keywords

Respiratory Mucosa, Vero Cells, Animals, Humans, Mesocricetus, Disease Models, Animal, Lactams, Nitriles, Leucine, Proline, Administration, Oral, Virus Replication, Cricetinae, A549 Cells, Chlorocebus aethiops, COVID-19, SARS-CoV-2, Coronavirus 3C Proteases, Viral Protease Inhibitors