Influenza A virus RNA-directed RNA polymerase subunit PB1 (PB1)

The Influenza A virus RNA-directed RNA polymerase subunit PB1 is the catalytic core of the viral heterotrimeric RNA-dependent RNA polymerase (RdRp) complex, which also includes the PA and PB2 subunits [7, 8, 12]. PB1 is responsible for both the replication of the viral RNA genome and the transcription of viral mRNAs using a 'cap-snatching' mechanism, where it utilizes capped RNA primers cleaved from host cellular mRNAs by the PA subunit [12, 20]. Beyond its enzymatic role, PB1 facilitates the assembly of the polymerase complex through high-affinity interactions with PA and PB2 and plays a role in evading the host's innate immune system by inducing the degradation of MAVS [11, 13, 15]. Due to its essential function and high sequence conservation across different influenza strains, PB1 is a primary target for antiviral development [4, 9]. Current therapeutic strategies include nucleoside analogs like favipiravir, which act as alternative substrates for PB1 to cause chain termination or lethal mutagenesis, as well as experimental small molecules and peptides designed to disrupt the critical protein-protein interfaces within the RdRp complex [2, 5, 6, 14].

Other names

Polymerase basic protein 1RNA-directed RNA polymerase catalytic subunitP1 proteinRNA-directed RNA polymerase subunit P1

Drugs targeting PB1 primarily act by inhibiting viral RNA synthesis through two main mechanisms: nucleoside analogs like favipiravir serve as alternative substrates that lead to premature chain termination or lethal mutagenesis during RNA polymerization [6, 12], while experimental inhibitors and peptides disrupt the essential protein-protein interactions between PB1 and the PA or PB2 subunits, preventing the assembly of a functional heterotrimeric polymerase complex [2, 5, 9, 11].