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

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. Natchus, George R. Painter, Kaori Sakamoto, Alexander L. Greninger and Richard K. Plemper ()
Additional contact information
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

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

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32045-1

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DOI: 10.1038/s41467-022-32045-1

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