Favipiravir as a potential countermeasure against neglected and emerging RNA viruses

Abstract

Favipiravir, also known as T-705, is an antiviral drug that has been approved in 2014 in Japan to treat pandemic influenza virus infections. The drug is converted intracellularly into its active, phosphoribosylated form, which is recognized as a substrate by the viral RNA-dependent RNA polymerase. Interestingly, besides its anti-influenza virus activity, this molecule is also able to inhibit the replication of flavi-, alpha-, filo-, bunya-, arena-, noro-, and of other RNA viruses, which include neglected and (re)emerging viruses for which no antiviral therapy is currently available. We will discuss the potential of favipiravir as a broad-spectrum countermeasure against infections caused by such neglected RNA viruses. Favipiravir has already been used off-label to treat patients infected with the Ebola virus and the Lassa virus. Because of the particular set-up of the clinical trials during these outbreaks, clear conclusions on the efficacy of favipiravir could not be made. For several viruses, it was demonstrated that the barrier of resistance development against favipiravir is high. Favipiravir has been shown to be well tolerated in healthy volunteers and in influenza virus-infected patients; however, caution is needed because of the teratogenic risks of this molecule. Because of its antiviral activity against different RNA viruses and its high barrier for resistance, the potential of favipiravir as a broad-spectrum antiviral seems promising, but safety and potency issues should be overcome before this drug or similar molecules could be used to treat large patient groups.