Influenza A virus polymerase: an attractive target for next-generation anti-influenza therapeutics

The influenza RNA-dependent RNA polymerase (RdRP) is conserved among different types of influenza virus, playing an important part in transcription and replication. In this regard, influenza RdRP is an attractive target for novel anti-influenza drug discovery. Herein, we will introduce the structural and functional information of influenza polymerase; and an overview of inhibitors targeting the PA endonuclease and PB2 cap-binding site is provided, along with the approaches utilized for identification of these inhibitors. The protein–protein interactions (PPIs) of the three polymerase subunits: PA, PB1 and PB2, are described based on the published crystal structures, and inhibitors targeting the PA–PB1 interaction are introduced briefly.