Further preclinical characterization of molnupiravir against SARS-CoV-2: Antiviral activity determinants and viral genome alteration patterns

• DOI: 10.1016/j.heliyon.2024.e30862
• Publication Date: 2024-05-08T16:50:01Z
• Authors: Paul-Rémi Petit; Franck Touret; Jean-Sélim Driouich; Maxime Cochin; Léa Luciani; Ornéllie Bernadin; Caroline Laprie; Géraldine Piorkowski; Laurent Fraisse; Peter Sjö; Charles E. Mowbray; Fanny Escudié; Ivan Scandale; Eric Chatelain; Xavier de Lamball...; Caroline Solas; Antoine Nougairède
• Keywords: 2019-20 coronavirus outbreak; Sars virus; Coronavirus

The SARS-CoV-2 pandemic has highlighted the need for broad-spectrum antiviral drugs to respond promptly viral emergence. We conducted a preclinical study of molnupiravir (MOV) against fully characterise its properties and mode action. activity different concentrations MOV was evaluated ex vivo on human airway epithelium (HAE) in hamster model at three escalating doses (150, 300 400 mg/kg/day) according regimens (preventive, pre-emptive curative). assessed loads infectious titres apical pole HAE lungs, trough concentration plasma lungs. To explore action MOV, entire genomes collected viruses were deep-sequenced. effectively reduced lungs treated animals. Early treatment after infection key factor efficacy, probably associated with high lung suggesting good accumulation lung. induced genomic alteration an increase number minority variants, predominant G A transitions. observed reduction replication mechanism leading lethal mutagenesis, supported by clinical trials showing humans, provide convincing basis further research as additional means fight COVID-19 other RNA viruses.