Polymerase basic protein 1 (PB1) (PB1)

The Polymerase basic protein 1 (PB1) is the catalytic subunit of the heterotrimeric RNA-dependent RNA polymerase (RdRp) complex in Influenza A virus, which also comprises the PA and PB2 subunits [4, 17]. PB1 is essential for viral survival as it mediates RNA chain elongation during both the transcription of viral mRNA and the replication of the viral genomic RNA [4, 13]. It contains highly conserved motifs characteristic of RdRps, making it a prime target for antiviral therapy [2, 12]. The antiviral drug favipiravir (T-705) is a well-known inhibitor that, in its active triphosphate form, competes with natural purine nucleotides for incorporation by PB1, resulting in premature chain termination or lethal mutagenesis of the viral genome [4, 8, 13]. Beyond its polymerase activity, the PB1 gene also encodes an accessory protein, PB1-F2, via an alternative reading frame; this protein enhances virulence by inducing host cell apoptosis and suppressing innate immune signaling [14, 15, 16]. Therapeutic challenges include the emergence of resistance mutations, such as the PB1 K229R substitution, which can be compensated for by mutations in other subunits like PA P653L to restore viral fitness [2, 8, 9].

Other names

RNA-directed RNA polymerase catalytic subunitPB1 proteinInfluenza A virus RNA polymerase PB1 subunitPolymerase basic protein 1

PB1 acts as the catalytic core of the viral RNA polymerase complex, facilitating RNA chain elongation. Drugs like favipiravir are recognized as purine analogs and incorporated into the nascent RNA strand, leading to chain termination or lethal mutagenesis. Additionally, experimental inhibitors target the protein-protein interaction interfaces between PB1 and the PA or PB2 subunits to prevent complex assembly.