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

The **influenza virus polymerase acidic subunit cap-dependent endonuclease** (PA endonuclease) is a component of the heterotrimeric influenza virus RNA-dependent RNA polymerase complex, consisting of the PB1, PB2, and PA subunits. The PA subunit contains the endonuclease active site that cleaves host pre-mRNA near the cap structure—a process known as *cap-snatching*—which is essential for synthesizing viral mRNAs. This enzymatic activity enables the virus to hijack host transcription machinery and is vital for viral replication. The PA endonuclease has been validated as a key drug target, with inhibitors such as baloxavir marboxil approved for clinical use. Mutations, notably I38T in the PA domain, can confer resistance to these drugs, underscoring its therapeutic importance and the need for ongoing surveillance of antiviral efficacy[4][6][7].

Other names

PA endonucleasecap-dependent endonuclease (CEN)influenza virus polymerase PA subunit

Inhibition of endonuclease activity: Drugs bind the active site of PA endonuclease and block cap-snatching, preventing viral mRNA synthesis and halting replication [4][6].