A peptide derived from the C-terminus of PB1 inhibits influenza virus replication by interfering with viral polymerase assembly

Efficient assembly of the influenza virus RNA-dependent RNA polymerase, a heterotrimeric complex formed by three subunits (PA, PB1 and PB2) is critical for virus replication and pathogenicity. Therefore, interfering with the assembly of the RNA-dependent RNA polymerase complex could offer novel and effective anti-influenza therapeutics. In the present study, we show that a short peptide derived from amino acids 731757 of PB1 (PB1731757) can disrupt the interaction between the C-terminal part of PB1 (denoted as PB1c corresponding to PB1676757) and the N-terminal part of PB2 (denoted as PB2n corresponding to PB2140). We further show that PB1731757 is capable of inhibiting viral polymerase activity and viral replication. Interestingly, we find that PB1731757 interacts with PB1c rather than PB2n. Furthermore, mutational analyses show that the hydrophobic sites of PB1c play an essential role in the PB1cPB1731757 interaction. The characterization of the inhibitory effect of PB1731757 on viral polymerase activity and viral replication could offer a potential target for anti-influenza drug development. Structured digital abstract PB2n physically interacts with PB1c by pull down (View interaction) PB2n and PB1c physically interact by bimolecular fluorescence complementation (View interaction) PB1 (731-757) physically interacts with PB1c by pull down (View interaction) PB1 (731-757) and PB1c physically interact by bimolecular fluorescence complementation (View Interaction: 1, 2, 3, 4, 5) [Structured digital abstract was added on 11 February 2013 after original online publication]