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

Rana Abdelnabi, Caroline S. Foo, Dirk Jochmans, Laura Vangeel, Steven De Jonghe, Patrick Augustijns, Raf Mols, Birgit Weynand, Thanaporn Wattanakul, Richard M. Hoglund, Joel Tarning, Charles E. Mowbray, Peter Sjö, Fanny Escudié, Ivan Scandale, Eric Chatelain and Johan Neyts ()
Additional contact information
Rana Abdelnabi: Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy
Caroline S. Foo: Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy
Dirk Jochmans: Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy
Laura Vangeel: Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy
Steven De Jonghe: Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy
Patrick Augustijns: KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery & Disposition
Raf Mols: KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery & Disposition
Birgit Weynand: KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research
Thanaporn Wattanakul: Mahidol University
Richard M. Hoglund: Mahidol University
Joel Tarning: Mahidol University
Charles E. Mowbray: Drugs for Neglected Diseases initiative
Peter Sjö: Drugs for Neglected Diseases initiative
Fanny Escudié: Drugs for Neglected Diseases initiative
Ivan Scandale: Drugs for Neglected Diseases initiative
Eric Chatelain: Drugs for Neglected Diseases initiative
Johan Neyts: Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy

Nature Communications, 2022, vol. 13, issue 1, 1-9

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28354-0

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