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

The influenza virus polymerase acidic (PA) cap-dependent endonuclease is a critical enzyme located in the N-terminal domain of the PA subunit of the influenza virus RNA-dependent RNA polymerase (RdRp) complex [1, 3, 8]. It plays a central role in the "cap-snatching" process, where it cleaves the 5'-capped primers from host cellular pre-mRNAs to initiate viral mRNA synthesis [3, 8, 11]. This activity is essential for viral replication and transcription, making it a high-value target for antiviral therapy [2, 7]. Baloxavir marboxil is the first-in-class drug that targets this endonuclease, effectively inhibiting viral proliferation by blocking the production of viral mRNA [3, 6, 14]. However, the emergence of resistance mutations, particularly the I38T substitution in the PA domain, poses a significant challenge to the long-term efficacy of these inhibitors [1, 9, 12].

Other names

PA endonucleaseInfluenza PA subunitCap-dependent endonuclease (CEN)Polymerase acidic protein N-terminal domainPA-Nter

Inhibition of the cap-dependent endonuclease activity of the viral RNA polymerase, preventing the "cap-snatching" process required for viral mRNA synthesis.