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

The Influenza A virus polymerase acidic (PA) protein cap-dependent endonuclease domain is a critical enzymatic component of the viral RNA-dependent RNA polymerase (RdRp) complex, which is essential for the replication of the influenza virus [1, 2]. This domain, located within the N-terminal region of the PA subunit (PA-Nter), is responsible for the 'cap-snatching' mechanism, a process where the virus cleaves host cellular pre-mRNAs to obtain capped primers for its own mRNA synthesis [2, 3]. Because this endonuclease activity is unique to the virus and has no direct human counterpart, it serves as a highly specific and effective target for antiviral intervention [2, 5]. The drug baloxavir marboxil (Xofluza) specifically targets this domain, inhibiting its catalytic activity and thereby halting viral transcription and replication [3]. While highly effective, the therapeutic utility of targeting this domain is challenged by the rapid emergence of resistance mutations, most notably the I38T substitution in the PA protein [5].

Other names

PA endonucleasePA-N terminal domainPANPolymerase acidic protein N-terminal domainCap-dependent endonuclease

Inhibition of the cap-dependent endonuclease activity of the PA subunit, which prevents the cleavage of host capped pre-mRNAs and thus blocks the initiation of viral mRNA synthesis (cap-snatching).