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

• DOI: 10.1038/s41467-022-32045-1
• Publication Date: 2022-07-29T19:04:06Z
• Authors: 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. Kaly...; Michael G. Natchus; George R. Painter; Kaori Sakamoto; Alexander L. Gren...; Richard K. Plemper
• Keywords: Mesocricetus

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 omicron is unknown. This study evaluates in human airway epithelium organoids, ferrets, a lethal Roborovski dwarf hamster model severe COVID-19-like lung injury. were equally inhibited by cells organoids. Treatment reduced shedding ferrets prevented transmission. Pathogenicity hamsters VOC-dependent highest for delta, gamma, omicron. All molnupiravir-treated survived, showing reduction virus load from one (delta) four (gamma) orders magnitude. effect size varied individual infected with significant males, not females. The recapitulates mixed trials alerts that benefit must be reassessed vivo evolve.