The mechanism of resistance to favipiravir in influenza

Favipiravir is a broad-spectrum antiviral that has shown promise in treatment of influenza virus infections, in particular due to the apparent lack of emergence of resistance mutations against the drug in cell culture or animal studies. We demonstrate here that a mutation in a conserved region of the viral RNA polymerase confers resistance to favipiravir in vitro and in cell culture. The resistance mutation has a cost to viral fitness, but this can be restored by a compensatory mutation in the polymerase. Our findings support the development of favipiravir-resistance diagnostic and surveillance testing strategies and reinforce the importance of considering combinations of therapies to treat influenza infections.