Influenza virus RNA polymerase subunit PB2 (PB2)

The Influenza virus RNA polymerase subunit PB2 is a critical component of the heterotrimeric RNA-dependent RNA polymerase (RdRp) complex, which also includes PB1 and PA subunits (UniProt P03428). PB2 is primarily responsible for the "cap-snatching" process, where it binds to the 5' methylated cap of host cellular pre-mRNAs (PubMed: 25119033). This binding allows the polymerase to use the host's RNA as a primer for viral mRNA synthesis, making it essential for viral replication (PubMed: 27903808). Beyond transcription, PB2 is a key determinant of host range and adaptation, often mutating to allow avian influenza viruses to replicate efficiently in human cells (PubMed: 24009512). Because PB2 lacks a human homolog, it is a highly attractive target for antiviral therapy (PubMed: 30135115). Drugs like pimodivir (VX-787) target the cap-binding pocket of PB2 to halt the viral life cycle (PubMed: 28808010). However, the high mutation rate of the influenza virus poses a significant challenge, as resistance can develop quickly under selective pressure (PubMed: 27903808). Clinical development of PB2 inhibitors has faced hurdles, including limited efficacy in hospitalized patients with severe disease (PubMed: 33161313). Despite these challenges, PB2 remains a focus for next-generation antivirals aimed at overcoming resistance to neuraminidase inhibitors.

Other names

Polymerase basic protein 2RNA-directed RNA polymerase subunit PB2PB2 subunitHost-range determinant PB2Influenza virus RNA polymerase PB2 protein

Inhibition of the cap-binding site of the PB2 subunit, preventing the recruitment of host capped pre-mRNAs and thereby blocking viral mRNA transcription (PubMed: 27903808).