Influenza A virus polymerase basic protein 2 (PB2) cap-binding domain (PB2-CBD)

The Influenza A virus polymerase basic protein 2 (PB2) cap-binding domain is a specialized structural motif within the PB2 subunit of the viral RNA-dependent RNA polymerase (RdRp) complex [UniProt: P03428]. Its primary biological role is to facilitate 'cap-snatching,' a process where the virus binds to the 5' 7-methylguanosine (m7G) cap of host cellular pre-mRNAs [PMID: 18463633]. This binding allows the viral polymerase to use the host's cap as a primer for its own mRNA synthesis, effectively hijacking the host's translation machinery. Because this mechanism is unique to the virus and essential for its replication, the PB2 cap-binding domain serves as a potent therapeutic target [PMID: 24855125]. Small molecule inhibitors like Pimodivir (VX-787) competitively bind to this domain, preventing host cap recognition and halting viral transcription [PMID: 27535943]. This target is particularly valuable for treating influenza infections that have developed resistance to neuraminidase inhibitors, though the emergence of specific PB2 mutations remains a clinical challenge.

Other names

PB2 cap-binding domainPolymerase basic protein 2 cap-binding domainInfluenza A virus PB2 subunitPB2 m7G cap-binding site

Inhibition of the cap-binding domain of the PB2 subunit, preventing the cap-snatching process required for viral mRNA synthesis.