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

Rana Abdelnabi, Caroline S. Foo, View ORCID ProfileDirk 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, Johan Neyts
doi: https://doi.org/10.1101/2021.11.04.467077
Rana Abdelnabi
1KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
2Global Virus Network, GVN, Baltimore, Maryland, USA
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Caroline S. Foo
1KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
2Global Virus Network, GVN, Baltimore, Maryland, USA
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Dirk Jochmans
1KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
2Global Virus Network, GVN, Baltimore, Maryland, USA
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  • ORCID record for Dirk Jochmans
Laura Vangeel
1KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
2Global Virus Network, GVN, Baltimore, Maryland, USA
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Steven De Jonghe
1KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
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Patrick Augustijns
3KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery & Disposition, Box 921, 3000 Leuven, Belgium
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Raf Mols
3KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery & Disposition, Box 921, 3000 Leuven, Belgium
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Birgit Weynand
4KU Leuven Department of Imaging and Pathology, Translational Cell and Tissue Research, B-3000
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Thanaporn Wattanakul
5Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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Richard M. Hoglund
5Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
6Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Joel Tarning
5Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
6Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Charles E. Mowbray
7Drugs for Neglected Diseases initiative, Geneva, Switzerland
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Peter Sjö
7Drugs for Neglected Diseases initiative, Geneva, Switzerland
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Fanny Escudié
7Drugs for Neglected Diseases initiative, Geneva, Switzerland
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Ivan Scandale
7Drugs for Neglected Diseases initiative, Geneva, Switzerland
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Eric Chatelain
7Drugs for Neglected Diseases initiative, Geneva, Switzerland
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Johan Neyts
1KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
2Global Virus Network, GVN, Baltimore, Maryland, USA
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  • For correspondence: johan.neyts@kuleuven.be
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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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 05, 2021.
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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, Johan Neyts
bioRxiv 2021.11.04.467077; doi: https://doi.org/10.1101/2021.11.04.467077
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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, Johan Neyts
bioRxiv 2021.11.04.467077; doi: https://doi.org/10.1101/2021.11.04.467077

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