Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model

Despite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we use a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics. When treatment is initiated before or simultaneously to infection, favipiravir has a strong dose effect, leading to reduction of infectious titers in lungs and clinical alleviation of the disease. Antiviral effect of favipiravir correlates with incorporation of a large number of mutations into viral genomes and decrease of viral infectivity. Antiviral efficacy is achieved with plasma drug exposure comparable with those previously found during human clinical trials. Notably, the highest dose of favipiravir tested is associated with signs of toxicity in animals. Thereby, pharmacokinetic and tolerance studies are required to determine whether similar effects can be safely achieved in humans. Favipiravir has broad-spectrum antiviral activity against a variety of RNA viruses. Here the authors investigate the safety, pharmacokinetics and anti-SARS-CoV-2 efficacy of different drug dosage in the a Syrian hamster model of infection and, combined with genetic analyses, they show that Favipiravir at high doses decrease viral infectivity while inducing the emergence of mutations in viral genomes, decreasing fitness.