Lethal mutagenesis as an antiviral strategy

Description Lethal mutagenesis of RNA viruses is a viable a ntiviral strategy but has unknown risks Viruses depend on the host cell to carry out much of their replication, with each offering only a few virus-specific targets for the development of antiviral therapies. This makes the development of broadly active antivirals difficult to conceptualize. Numerous RNA viruses—including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus, and Chikungunya virus—have led to recent epidemics, highlighting the need for effective antiviral drugs that can be enlisted quickly. Some years ago, a broadly applicable antiviral strategy was proposed in which a slight increase in the error rate of a rapidly replicating RNA virus would overwhelm the capacity to remove deleterious mutations, driving the viral population to extinction; this strategy is called lethal mutagenesis (1). Although the antivirals ribavirin and favipiravir were developed with this strategy in mind, the recent development of the much more potent molnupiravir to treat SARS-CoV-2 highlights the unknown risks to the host that this strategy entails.