Towards broader-spectrum direct-acting antivirals against RNA viruses.

Small molecule antiviral drugs have transformed the management of infections such as those caused by HIV, hepatitis B virus, hepatitis C virus, herpesviruses and influenza viruses. Effective antiviral therapeutics remain unavailable for many other often life-threatening viral infections, many of which are caused by RNA viruses. The development of potent, safe and orally available antivirals is therefore essential both to address current unmet medical needs and to strengthen epidemic and pandemic preparedness. In this Review, we discuss the rationale for building a diversified portfolio of broader-spectrum antivirals against RNA viruses with activity spanning multiple genera, entire families or even crossing viral families. We provide a non-exhaustive overview of approved and investigational antiviral agents active against RNA viruses and discuss the biological determinants that underlie their antiviral spectrum. Finally, we outline the clinical development frameworks required to accelerate the evaluation of such drugs, in particular in the context of outbreaks.