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SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model

Author

Listed:
  • Carolin M. Lieber

    (Georgia State University)

  • Robert M. Cox

    (Georgia State University)

  • Julien Sourimant

    (Georgia State University)

  • Josef D. Wolf

    (Georgia State University)

  • Kate Juergens

    (University of Washington)

  • Quynh Phung

    (University of Washington)

  • Manohar T. Saindane

    (Emory University)

  • Meghan K. Smith

    (Emory University)

  • Zachary M. Sticher

    (Emory University)

  • Alexander A. Kalykhalov

    (Emory University)

  • Michael G. Natchus

    (Emory University)

  • George R. Painter

    (Emory University)

  • Kaori Sakamoto

    (University of Georgia)

  • Alexander L. Greninger

    (University of Washington)

  • Richard K. Plemper

    (Georgia State University)

Abstract

SARS-CoV-2 variants of concern (VOC) have triggered infection waves. Oral antivirals such as molnupiravir promise to improve disease management, but efficacy against VOC delta was questioned and potency against omicron is unknown. This study evaluates molnupiravir against VOC in human airway epithelium organoids, ferrets, and a lethal Roborovski dwarf hamster model of severe COVID-19-like lung injury. VOC were equally inhibited by molnupiravir in cells and organoids. Treatment reduced shedding in ferrets and prevented transmission. Pathogenicity in dwarf hamsters was VOC-dependent and highest for delta, gamma, and omicron. All molnupiravir-treated dwarf hamsters survived, showing reduction in lung virus load from one (delta) to four (gamma) orders of magnitude. Treatment effect size varied in individual dwarf hamsters infected with omicron and was significant in males, but not females. The dwarf hamster model recapitulates mixed efficacy of molnupiravir in human trials and alerts that benefit must be reassessed in vivo as VOC evolve.

Suggested Citation

  • Carolin M. Lieber & Robert M. Cox & Julien Sourimant & Josef D. Wolf & Kate Juergens & Quynh Phung & Manohar T. Saindane & Meghan K. Smith & Zachary M. Sticher & Alexander A. Kalykhalov & Michael G. N, 2022. "SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32045-1
    DOI: 10.1038/s41467-022-32045-1
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    Cited by:

    1. Juan Liu & Fengfeng Mao & Jianhe Chen & Shuaiyao Lu & Yonghe Qi & Yinyan Sun & Linqiang Fang & Man Lung Yeung & Chunmei Liu & Guimei Yu & Guangyu Li & Ximing Liu & Yuansheng Yao & Panpan Huang & Dongx, 2023. "An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Robert M. Cox & Carolin M. Lieber & Josef D. Wolf & Amirhossein Karimi & Nicole A. P. Lieberman & Zachary M. Sticher & Pavitra Roychoudhury & Meghan K. Andrews & Rebecca E. Krueger & Michael G. Natchu, 2023. "Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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