SARS-CoV-2 variants of concern (VOC) have initiated separate infection waves in the coronavirus disease 2019 (COVID-19) pandemic, pinnacling in currently all-time high incidence rates of VOC omicron. Orally available direct-acting antivirals like molnupiravir assure to improve disease management and limit SARS-CoV-2 spread. However, the efficacy of molnupiravir against VOC delta was questioned established on clinical trial results and its potency against omicron remains unidentified. 

A study evaluated molnupiravir against a panel of relevant VOC utilizing three efficacy models: 

• primary human airway epithelium organoids, 
• the ferret model of upper respiratory disease, 
• A lethal Roborovski dwarf hamster efficacy model of acute lung injury resembling severe COVID-19. 

And observed the following-

• All VOC showed equal and efficient inhibition by molnupiravir in cultured cells and organoids.
• Upper respiratory VOC shedding in ferrets was reduced and viral transmission was prevented with the treatment.
• The dwarf hamsters showed VOC-dependent Pathogenicity, which was highest for gamma, omicron, and delta with fulminant lung histopathology. 
• Oral molnupiravir initiated 12 hours after an infection caused complete survival of treated dwarf hamsters independent of challenge VOC. 
• Yet, reduction in lung virus varied VOC-dependently, ranging from one (delta) to four (gamma) orders of magnitude likened to vehicle-treated animals. 
• Dwarf hamsters infected with VOC omicron demonstrated marked individual variation in response to treatment. 
• Treated males had marked virus load reduction but not females. 

This dwarf hamster model summarize the mixed efficacy of molnupiravir seen in human trials and indicates that the therapeutic benefit of approved antivirals must be continuously reassessed in vivo as new VOC emerge.

Source- bioRxiv 2022.02.04.479171; doi: https://doi.org/10.1101/2022.02.04.479171