The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern
Abdelnabi et al.,
The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants..,
bioRxiv, doi:10.1101/2021.11.04.467077 (Preprint)
In Vitro and hamster study showing paxlovid component PF-07321332 effective against four variants of concern, inibits replication of the alpha variant in primary human airway epithelial cells, protected Syrian hamsters against intranasal infection with B.1.351 and B.1.617.2, and prevented transmission from B.1.617.2 infected animals.
Abdelnabi et al., 5 Nov 2021, preprint, 17 authors.
Abstract: bioRxiv preprint doi: https://doi.org/10.1101/2021.11.04.467077; this version posted November 5, 2021. The copyright holder for this
preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
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The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV2 variants of concern
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Rana Abdelnabi1,2, Caroline S. Foo1,2, Dirk Jochmans1,2, Laura Vangeel1,2, Steven De Jonghe1, Patrick
Augustijns3, Raf Mols3, Birgit Weynand4, Thanaporn Wattanakul5, Richard M. Hoglund5,6, Joel
Tarning5,6, Charles E. Mowbray7, Peter Sjö7, Fanny Escudié7, Ivan Scandale7, Eric Chatelain7, Johan
Neyts1,2*.
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1. KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for
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Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium.
2. Global Virus Network, GVN, Baltimore, Maryland, USA.
3. KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery &
Disposition, Box 921, 3000 Leuven, Belgium.
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4. KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research, B-3000
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5. Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University,
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Bangkok, Thailand
6. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of
Oxford, Oxford, UK
7. Drugs for Neglected Diseases initiative, Geneva, Switzerland
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*To whom correspondence may be addressed. Prof. Johan Neyts, Email: johan.neyts@kuleuven.be.
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bioRxiv preprint doi: https://doi.org/10.1101/2021.11.04.467077; this version posted November 5, 2021. The copyright holder for this
preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
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Abstract
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There is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-
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07321332 (PF-332), a potent inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed
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orally and that is in clinical development. We here report that PF-332 exerts equipotent in vitro activity
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against the four SARS-CoV-2 variants of concerns (VoC) and that it can completely arrest replication of
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the alpha variant in primary human airway epithelial cells grown at the air-liquid interface. Treatment
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of Syrian Golden hamsters with PF-332 (250 mg/kg, twice daily) completely protected the animals
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against intranasal infection with the beta (B.1.351) and delta (B.1.617.2) SARS-CoV-2 variants.
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Moreover, treatment of SARS-CoV-2 (B.1.617.2) infected animals with PF-332 completely prevented
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transmission to untreated co-housed sentinels.
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Keywords
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SARS-CoV-2; PF-07321332, Variants of concerns (VoC); Antivirals; Mpro inhibitors,
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bioRxiv preprint doi: https://doi.org/10.1101/2021.11.04.467077; this version posted November 5, 2021. The copyright holder for this
preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
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