Polymerase basic protein 1 (PB1)

Polymerase basic protein 1 (PB1) is the catalytic core and structural backbone of the heterotrimeric influenza virus RNA-dependent RNA polymerase (RdRp) complex, which also includes the PB2 and PA subunits [1, 4]. It is responsible for the synthesis of both viral mRNA and genomic RNA (vRNA and cRNA), utilizing a unique cap-snatching mechanism for transcription where it uses host-derived primers [9, 14]. PB1 contains highly conserved motifs essential for RNA polymerization, making it a critical determinant of viral replication, fitness, and host adaptation [4, 12]. Due to its essential function and high sequence conservation across various influenza A and B strains, PB1 is a primary target for antiviral therapy [1, 5]. Current therapeutic strategies include nucleoside analogues like favipiravir that inhibit its catalytic activity by acting as a chain terminator or inducing lethal mutagenesis [1, 11, 12]. Additionally, experimental small molecules are being developed to disrupt its protein-protein interactions with PA or PB2, thereby preventing the assembly of the functional polymerase complex [2, 7, 8].

Other names

RNA-directed RNA polymerase catalytic subunitRNA-directed RNA polymerase subunit P1PB1 subunitInfluenza virus PB1

RNA-dependent RNA polymerase inhibition through chain termination or lethal mutagenesis, and disruption of viral polymerase complex assembly via protein-protein interaction (PPI) inhibition.