Influenza virus RNA polymerase subunit PA (PA) (PA)

The Influenza virus RNA polymerase subunit PA is an essential component of the viral replication machinery, forming a heterotrimeric complex with the PB1 and PB2 subunits (UniProt P03433). Its primary role involves the "cap-snatching" mechanism, where its N-terminal domain acts as a manganese-dependent endonuclease to cleave the 5' cap from host pre-mRNAs (PubMed PMC6466057). These capped fragments then serve as primers for the synthesis of viral mRNAs by the PB1 subunit. Because this process is unique to the virus and critical for its life cycle, the PA subunit is a high-value therapeutic target. Baloxavir marboxil, a small-molecule inhibitor, specifically targets the PA endonuclease site to prevent viral transcription and replication (FDA Xofluza Label). Clinical use of such inhibitors requires monitoring for resistance-associated substitutions, particularly at position I38 of the PA protein, which can significantly reduce drug susceptibility (PubMed PMC7107411).

Other names

Polymerase acidic proteinPA proteinRNA-directed RNA polymerase subunit PAP3 protein

Cap-dependent endonuclease inhibitor