Influenza polymerase PA subunit (PA)

The influenza polymerase PA subunit is one of three essential subunits (PA, PB1, PB2) that compose the viral RNA-dependent RNA polymerase complex of influenza A and B viruses[1][5][7]. The PA protein is a multifunctional enzyme of approximately 716 amino acids, playing a central role in both the transcription and replication of the viral genome by forming a functional heterotrimer with PB1 and PB2 subunits[1][5][7]. The N-terminal domain of PA possesses endonuclease activity, required for the 'cap-snatching' mechanism—where host mRNA is cleaved and its capped fragment used as a primer for viral mRNA synthesis[1][6][7]. The C-terminal domain interacts with PB1, stabilizing the polymerase complex and facilitating RNA synthesis[2][5]. PA is also subject to posttranslational modifications such as phosphorylation, which modulate its function and, consequently, viral replication[4]. Inhibition of the PA endonuclease domain by small molecule drugs represents a clinically validated antiviral strategy, exemplified by the approval of baloxavir marboxil. Resistance to these drugs can arise via defined mutations in PA, making ongoing surveillance critical. PA is well validated as a therapeutic target for anti-influenza drugs, with a central role in the viral replication cycle and transmission dynamics[1][4][5][7].

Other names

Polymerase acidic proteinPA proteinPA subunit of influenza virus polymerase complexSegment 3 protein (Influenza virus)

Inhibition of endonuclease activity (blocks cap-snatching and viral mRNA synthesis) Disruption of viral RNA synthesis (by inhibiting the formation or activity of the heterotrimeric polymerase)