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

Author

Listed:
  • Rana Abdelnabi

    (Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy
    Global Virus Network, GVN)

  • Caroline S. Foo

    (Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy
    Global Virus Network, GVN)

  • Dirk Jochmans

    (Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy
    Global Virus Network, GVN)

  • Laura Vangeel

    (Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy
    Global Virus Network, GVN)

  • 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
    University of Oxford)

  • Joel Tarning

    (Mahidol University
    University of Oxford)

  • 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
    Global Virus Network, GVN)

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.

Suggested Citation

  • 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 & Charle, 2022. "The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28354-0
    DOI: 10.1038/s41467-022-28354-0
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    References listed on IDEAS

    as
    1. Zhenming Jin & Xiaoyu Du & Yechun Xu & Yongqiang Deng & Meiqin Liu & Yao Zhao & Bing Zhang & Xiaofeng Li & Leike Zhang & Chao Peng & Yinkai Duan & Jing Yu & Lin Wang & Kailin Yang & Fengjiang Liu & Re, 2020. "Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors," Nature, Nature, vol. 582(7811), pages 289-293, June.
    2. Robbert Boudewijns & Hendrik Jan Thibaut & Suzanne J. F. Kaptein & Rong Li & Valentijn Vergote & Laura Seldeslachts & Johan Weyenbergh & Carolien Keyzer & Lindsey Bervoets & Sapna Sharma & Laurens Lie, 2020. "STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    3. Goran Kokic & Hauke S. Hillen & Dimitry Tegunov & Christian Dienemann & Florian Seitz & Jana Schmitzova & Lucas Farnung & Aaron Siewert & Claudia Höbartner & Patrick Cramer, 2021. "Mechanism of SARS-CoV-2 polymerase stalling by remdesivir," Nature Communications, Nature, vol. 12(1), pages 1-7, December.
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    Cited by:

    1. Maki Kiso & Yuri Furusawa & Ryuta Uraki & Masaki Imai & Seiya Yamayoshi & Yoshihiro Kawaoka, 2023. "In vitro and in vivo characterization of SARS-CoV-2 strains resistant to nirmatrelvir," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    2. Maki Kiso & Seiya Yamayoshi & Shun Iida & Yuri Furusawa & Yuichiro Hirata & Ryuta Uraki & Masaki Imai & Tadaki Suzuki & Yoshihiro Kawaoka, 2023. "In vitro and in vivo characterization of SARS-CoV-2 resistance to ensitrelvir," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    3. Rana Abdelnabi & Dirk Jochmans & Kim Donckers & Bettina Trüeb & Nadine Ebert & Birgit Weynand & Volker Thiel & Johan Neyts, 2023. "Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in female Syrian hamsters and retains partial susceptibility to treatment," Nature Communications, Nature, vol. 14(1), pages 1-7, December.

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