Influenza virus PA-PB1 polymerase protein-protein interaction (PA-PB1 PPI) (PA-PB1 PPI)

The Influenza virus PA-PB1 polymerase protein-protein interaction is a critical structural interface within the viral RNA-dependent RNA polymerase (RdRp) complex, which consists of the PA, PB1, and PB2 subunits (Muratore et al., 2012, Antiviral Research). This interaction specifically involves the C-terminal domain of the PA subunit (PA_C) and the N-terminal 25 amino acids of the PB1 subunit (PB1_N), and it is essential for the assembly and stability of the functional heterotrimer (UniProt P03433, P03431). Because the RdRp is responsible for both the replication and transcription of the viral genome, disrupting this interaction effectively halts the viral life cycle (Wunderlich et al., 2009, AAC). This interface is highly conserved across different influenza A virus strains, making it an attractive target for broad-spectrum antiviral therapy (Massari et al., 2016, J. Med. Chem.). Small molecules and peptidomimetics designed to inhibit this interaction prevent the formation of the active polymerase complex, thereby reducing viral load. Unlike traditional neuraminidase inhibitors, targeting the PA-PB1 PPI offers a novel mechanism that may overcome existing drug resistance.

Other names

PA-PB1 interfaceInfluenza polymerase complex assemblyPA-PB1 interactionPA-PB1 interface interaction

Inhibition of the protein-protein interaction between the C-terminal domain of the PA subunit and the N-terminal domain of the PB1 subunit, preventing the assembly of the functional heterotrimeric polymerase complex.