Influenza Virus Endonuclease Domain (PA-Nter)

The influenza virus endonuclease domain is an essential subdomain of the viral RNA-dependent RNA polymerase complex. It is located within the N-terminal domain of the PA subunit and is responsible for cleaving host pre-mRNAs to generate primers required for viral mRNA synthesis, a process known as "cap-snatching." This activity is crucial for the transcription and replication of the viral genome and makes the endonuclease domain a highly attractive target for antiviral drug development. The active site contains conserved residues that coordinate two divalent metal ions (typically manganese or magnesium), which are essential for catalytic activity. Small molecule inhibitors, such as L-742,001 and baloxavir marboxil, can bind directly to this endonuclease active site. Resistance mutations map directly within this region.

Other names

PA N-terminal domainPANPA endonuclease

Inhibition of endonuclease activity, preventing viral mRNA synthesis