Influenza A virus RNA-directed RNA polymerase complex (RdRp)

The Influenza A virus RNA-directed RNA polymerase (RdRp) complex is a heterotrimeric enzyme essential for the replication and transcription of the viral genome. It consists of three subunits: Polymerase Acidic (PA), Polymerase Basic 1 (PB1), and Polymerase Basic 2 (PB2), which work coordinately within the nucleus of the host cell (UniProt: P03433, P03431, P03428). The complex performs a unique "cap-snatching" process where it steals 5' capped primers from host cellular pre-mRNAs to initiate viral mRNA synthesis (PubMed: 30713153). Because this machinery is distinct from host cell polymerases, it is a primary target for antiviral drugs such as baloxavir marboxil, which inhibits the PA endonuclease, and favipiravir, which acts as a chain terminator (PubChem: CID 124081904). Targeting this complex is critical for treating severe influenza and managing pandemic threats, although the rapid evolution of the virus can lead to drug resistance (NIH: StatPearls).

Other names

Influenza A virus RNA-dependent RNA polymeraseFluPolPA-PB1-PB2 complex3P complexInfluenza A virus polymerase complex

Inhibition of the cap-dependent endonuclease activity (PA subunit), inhibition of the cap-binding site (PB2 subunit), or acting as a nucleoside analogue to cause chain termination and lethal mutagenesis during RNA synthesis.