Influenza virus polymerase subunit PB2 (PB2)

The Influenza virus polymerase subunit PB2 is a critical component of the heterotrimeric RNA-dependent RNA polymerase (RdRp) complex, which also includes the PB1 and PA subunits. PB2 is responsible for the 'cap-snatching' mechanism, in which it binds to the 5'-methylguanosine cap of host cellular pre-mRNAs. This captured cap is then used as a primer for the synthesis of viral mRNA. Because this process is essential for viral protein expression and is unique to the virus, PB2 has emerged as a high-value therapeutic target. Small molecule inhibitors like pimodivir target the cap-binding pocket of PB2, effectively halting viral replication early in the infection cycle. While effective in clinical trials against Influenza A, the primary challenge remains the rapid selection of resistant variants and the subunit's lack of conservation in Influenza B strains. Understanding PB2's role in host-range restriction and its interactions with host nuclear import machinery also provides insights into zoonotic transmission and pandemic potential.

Other names

Polymerase basic protein 2RNA-directed RNA polymerase subunit PB2PB2 proteinCap-binding protein PB2

Inhibition of the cap-binding domain of the PB2 subunit to prevent the 'cap-snatching' process required for viral mRNA synthesis.