Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond

Flaviviruses, including dengue and Zika viruses, are of substantial public health concern. Klein and colleagues review the development of broad-spectrum antiviral agents that would target many of the known and potentially unknown flaviviruses. The benefits and caveats of molecules that target either viral proteins or host mechanisms exploited by these viruses are discussed. Infections with flaviviruses, such as dengue, West Nile virus and the recently re-emerging Zika virus, are an increasing and probably lasting global risk. This Review summarizes and comments on the opportunities for broad-spectrum agents that are active against multiple flaviviruses. Broad-spectrum activity is particularly desirable to prepare for the next flaviviral epidemic, which could emerge from as-yet unknown or neglected viruses. Potential molecular targets for broad-spectrum antiflaviviral compounds include viral proteins, such as the viral protease or polymerase, and host targets that are exploited by these viruses during entry and replication, including α-glucosidase and proteins involved in nucleoside biosynthesis. Numerous compounds with broad-spectrum antiviral activity have already been identified by target-specific or phenotypic assays. For other compounds, broad-spectrum activity can be anticipated because of their mode of action and molecular targets.