Antiviral therapies on the horizon for influenza

•The existing influenza drugs suffer from variable efficacy and risk of resistance.•Several new inhibitors of diverse viral targets are in clinical trials.•Broadly neutralizing antibodies directing the hemagglutinin are being developed.•For small molecules, the viral polymerase and nucleoprotein are two main targets.•Entirely new influenza drugs will likely become available in the next decade.

Adequate response to severe influenza infections or pandemic outbreaks requires two complementary strategies: preventive vaccination and antiviral therapy. The existing influenza drugs, M2 blockers and neuraminidase inhibitors, show modest clinical efficacy and established or potential resistance. In the past three years, several new agents have entered the clinical pipeline and already yielded some promising data from Phase 2 trials. For two main categories, that is, the broadly neutralizing anti-hemagglutinin antibodies and small-molecule inhibitors of the viral polymerase complex, crystallography was instrumental to guide drug development. These structural insights also aid to expand the activity spectrum towards influenza A plus B viruses, or conceive nucleoprotein or polymerase assembly inhibitors. The practice of influenza therapy should radically change in the next decade.