SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model.
Carolin M LieberRobert M CoxJulien SourimantJosef D WolfKate JuergensQuynh PhungManohar T SaindaneMeghan K SmithZachary M SticherAlexander A KalykhalovMichael G NatchusGeorge R PainterKaori SakamotoAlexander L GreningerRichard K PlemperPublished in: Nature communications (2022)
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.
Keyphrases
- sars cov
- induced pluripotent stem cells
- endothelial cells
- respiratory syndrome coronavirus
- coronavirus disease
- induced apoptosis
- early onset
- copy number
- gene expression
- combination therapy
- pluripotent stem cells
- drug induced
- staphylococcus aureus
- dna methylation
- cell death
- big data
- genome wide
- signaling pathway
- deep learning
- replacement therapy