Identification of influenza virus inhibitors which disrupt of viral polymerase protein–protein interactions

Due to their ability to rapidly mutate, influenza viruses quickly develop resistance against many antiviral substances, leading to an urgent need for new compounds. The trimeric viral polymerase complex, a major target for the development of new inhibitors, must be assembled from the PB1, PB2, and PA subunits for successful infection. Here, we describe ELISA-based assays which allow the identification of peptides which impair polymerase complex formation. Since the protein–protein interaction domains of the viral polymerase are highly conserved, these inhibitors are also predicted to be active against a broad range of influenza strains. Using this method, identification of small molecules and lead compounds against influenza A and B viruses should be feasible.