Influenza virus polymerase acidic protein endonuclease (PA (polymerase acidic))

The influenza virus polymerase acidic protein endonuclease (abbreviated as PA) is a critical enzyme within the heterotrimeric influenza virus RNA-dependent RNA polymerase complex, which also includes the PB1 and PB2 subunits. PA contains an N-terminal endonuclease domain (PAN) essential for the "cap-snatching" mechanism, by which the virus cleaves host pre-mRNAs to prime viral mRNA synthesis. This activity is necessary for both viral genome replication and transcription, making PA indispensable for the influenza virus life cycle. The endonuclease active site is a validated drug target, with the first approved inhibitor being baloxavir marboxil, which directly inhibits PA's endonuclease function, thereby blocking viral replication[1][2][3][4][5]. The PA protein also interacts structurally and functionally with the PB1 and PB2 subunits, facilitating multiple steps of viral RNA processing[1][2][3]. Potential therapeutic challenges include resistance to endonuclease inhibitors and limited breadth of available drugs targeting this enzyme[4].

Other names

polymerase acidic proteinPA subunitpolymerase acidic endonucleasePAN domainP3 (in influenza C virus)

Inhibition of endonuclease activity (prevents cap-snatching and subsequent viral mRNA synthesis)