Influenza virus polymerase PA subunit cap-dependent endonuclease (PA-CEN)

The influenza virus polymerase PA subunit cap-dependent endonuclease is a vital enzymatic component of the viral RNA-dependent RNA polymerase complex, which also includes the PB1 and PB2 subunits (UniProt) [15]. Its primary biological function is to facilitate 'cap-snatching,' a process where the enzyme cleaves the 5' methylated cap from host cell pre-mRNAs to use as a primer for viral mRNA transcription (Benchchem) [6], (PLOS Pathogens) [7]. This mechanism is essential for the virus to produce stable, translatable mRNA using the host's cellular machinery (Patsnap Synapse, 2024) [2]. Because this process is unique to the virus and highly conserved across influenza A and B strains, it serves as a potent therapeutic target (PubChem, NIH) [5]. Baloxavir marboxil, a first-in-class antiviral, acts by inhibiting this endonuclease activity, thereby halting viral replication and reducing the duration of symptoms (ChemicalBook, 2023) [3]. However, the emergence of resistance, particularly through the I38T mutation in the PA subunit, remains a significant clinical challenge (Biochemistry - ACS Publications) [19]. Monitoring viral load and specific genetic markers is crucial for assessing treatment efficacy and the development of resistance (Frontiers, 2025) [16].

Other names

PA endonucleasePolymerase acidic protein endonucleaseInfluenza A virus PA subunitInfluenza B virus PA subunitPA-N domain

Inhibition of the cap-dependent endonuclease activity of the PA subunit, preventing the 'cap-snatching' process required for viral mRNA synthesis (Patsnap Synapse, 2024) [2], (PubChem, NIH) [5].