Influenza virus RNA-dependent RNA polymerase (FluPol)

The **influenza virus RNA-dependent RNA polymerase** (commonly abbreviated as **FluPol**) is an essential and multifunctional enzyme complex of negative-sense, single-stranded influenza viruses. This heterotrimeric complex is composed of three subunits: PA (polymerase acidic protein), PB1 (polymerase basic protein 1), and PB2 (polymerase basic protein 2). FluPol performs all steps of viral RNA genome synthesis, including the transcription of capped viral mRNAs through a cap-snatching mechanism (where it cleaves 5′ caps from nascent host mRNAs, using PA endonuclease and PB2 cap-binding domains) as well as replication of full-length viral RNA. Its function relies on tight interactions both within its subunits and with viral nucleoprotein (NP) and various host cell factors, which are often required for determining species specificity and polymerase activity. FluPol is a validated antiviral drug target, as several small-molecule inhibitors (notably baloxavir and favipiravir) have been clinically approved or are under development, aimed at interfering with its enzymatic activities or assembly. Adaptation, transmission, and resistance are closely linked to mutations within the subunits, especially PB2. Safety challenges with therapeutics against FluPol include the risk of resistance selection and off-target effects on host nuclear functions[2][3][5][7].

Other names

Influenza polymeraseInfluenza polymerase complexFluPolInfluenza RdRpViral polymerase (PA/PB1/PB2)RNA-dependent RNA polymerase of influenza

Inhibition of cap-dependent endonuclease activity (e.g., baloxavir), Inhibition of RNA-dependent RNA polymerase activity (e.g., favipiravir), Inhibition of cap-binding (targeting PB2 subunit), Disruption of protein–protein interactions in polymerase assembly