Antivirals targeting the polymerase complex of influenza viruses.

Current influenza antivirals have limitations with regard to their effectiveness and the potential emergence of resistance. Encouragingly, several new compounds which inhibit the polymerase of influenza viruses have recently been shown to have enhanced pre-clinical and clinical effectiveness compared to the neuraminidase inhibitors, the mainstay of influenza antiviral therapy over the last two decades. In this review we focus on four compounds which inhibit polymerase function, baloxavir marboxil, favipiravir, pimodivir and AL-794 and discuss their clinical and virological effectiveness, their propensity to select for resistance and their potential for future combination therapy with the most commonly used neuraminidase inhibitor, oseltamivir. • Antiviral compounds targeting components of the polymerase complex PB1, PB2, and PA, are undergoing clinical investigation. • Baloxavir targets endonuclease activity of the PA polymerase subunit and was recently liscensed in Japan and USA for the treatment of influenza A and B viruses. • Favipiravir, a broad spectrum antiviral compound inhibits viral RNA polymerases and has limited licensure in Japan. • Pimodivir targets PB2 subunit of influenza A viruses preventing binding to 7-methyl GTP cap structures. • AL-794 binds to the endonuclease domain of PA but is no longer being evaluated for clinical use. [ABSTRACT FROM AUTHOR]