Influenza A virus RNA-directed RNA polymerase subunit PA (PA)

The Influenza A virus RNA-directed RNA polymerase subunit PA is one of three essential proteins forming the viral RNA-dependent RNA polymerase (RdRp) complex, alongside PB1 and PB2 (UniProt: P03481). The PA subunit is primarily characterized by its N-terminal endonuclease domain, which executes the "cap-snatching" mechanism (PubMed: 30644013). In this process, the subunit cleaves the 5'-methylguanosine cap from host cellular pre-mRNAs, which the virus then uses as a primer for its own mRNA synthesis (NCBI: NBK541060). Because this function is vital for viral replication and has no direct human counterpart, it is a high-priority target for antiviral drug development. Baloxavir marboxil is a first-in-class drug that specifically inhibits the PA endonuclease activity, providing a potent treatment option for acute uncomplicated influenza (FDA: Xofluza Label). Monitoring for mutations such as I38T in the PA subunit is critical, as they can significantly reduce drug susceptibility (PubMed: 30179581).

Other names

Polymerase acidic proteinPA proteinP3 proteinRNA-directed RNA polymerase subunit PA

Inhibition of the cap-dependent endonuclease activity of the PA subunit, which prevents the cleavage of host cellular pre-mRNAs and subsequent priming of viral mRNA synthesis (cap-snatching).