Influenza RNA-dependent RNA polymerase (FluPol)

Influenza RNA-dependent RNA polymerase (FluPol) is a critical, multifunctional enzyme required for the replication and transcription of the influenza virus RNA genome[1][2][3][4][5]. This polymerase is a heterotrimer composed of three subunits: polymerase basic 1 (PB1), polymerase basic 2 (PB2), and polymerase acidic (PA, also called P3 in influenza C virus)[1][2][3][4][5]. PB1 forms the core catalytic domain, PB2 contains the cap-binding domain necessary for “cap-snatching,” and PA harbors an endonuclease domain[1][2][3]. The enzyme operates in conjunction with viral ribonucleoprotein complexes and interacts with multiple host and viral factors[1][2]. Its structural conformational flexibility is essential for accommodating its diverse functions and adapting to different host species, which is a key determinant of influenza virus virulence and host range[1][2][3][5]. FluPol is a validated therapeutic target for direct-acting antivirals, such as baloxavir marboxil, although drug resistance can develop through point mutations in polymerase genes[1][5]. Thus, the influenza RNA-dependent RNA polymerase is central to viral replication, pathogenesis, and the development of new antiviral strategies.

Other names

Influenza virus RNA polymeraseFluPolRNA-directed RNA polymeraseviral RNA polymeraseRdRp

Inhibition of polymerase catalytic activity blocks viral RNA replication and transcription; Inhibition of endonuclease activity blocks cap-snatching, preventing initiation of viral mRNA synthesis; Nucleoside analog incorporation causing chain termination or mutagenesis