Influenza A virus polymerase acidic protein cap-dependent endonuclease domain (PA-Nter)

The Influenza A virus polymerase acidic (PA) protein cap-dependent endonuclease domain is a critical component of the viral RNA-dependent RNA polymerase (RdRp) complex (UniProt P03433). This domain, located at the N-terminus of the PA subunit (PA-Nter), is responsible for the cap-snatching process, where it cleaves the 5' methylated cap from host cellular pre-mRNAs (Dias et al., Nature 2009). These stolen caps serve as primers for the synthesis of viral mRNA, making the endonuclease essential for viral replication. Because this mechanism is unique to the virus and lacks a direct human homolog, it represents a highly specific therapeutic target. Drugs like baloxavir marboxil target this site by chelating the divalent metal ions (manganese or magnesium) required for the enzyme's catalytic activity (Noshi et al., Antiviral Res 2018). Inhibition of this domain effectively halts the production of viral proteins and the spread of the infection within the host (FDA, Xofluza Label).

Other names

PA endonucleaseInfluenza A virus PA subunit N-terminal domainCap-dependent endonucleasePA-CEN

Inhibition of the cap-dependent endonuclease activity of the PA subunit, which prevents the virus from snatching the 5' cap from host pre-mRNAs, thereby blocking viral mRNA synthesis and replication.