Current and novel antiviral strategies for influenza infection

Influenza A and B viruses are major causes for respiratory infections in children and adults. Viral and host factors determine clinical manifestations which range from self resolving uncomplicated infections, severe viral or bacterial secondary pneumonia, to death. Emergence of transmissible resistant variants and time-dependent effectiveness are the major challenges for the currently approved antivirals, M2 ion channel blockers and neuraminidase (NA) inhibitors. Favipiravir that inhibits the RNA-dependent RNA polymerase of multiple RNA viruses is approved in Japan against influenza strains resistant to available antivirals. With expanded knowledge on viral nucleoprotein (NP) and polymerase structures, novel small molecule inhibitors targeting NP oligomer formation, PA endonuclease domain, and the PB2 cap-binding domain are being developed. Combination therapy with different antiviral compounds or with host immune response modulators may further benefit clinical outcomes.