Zika virus non-structural protein 5 RNA-dependent RNA polymerase (NS5 RdRp) (ZIKV NS5 RdRp)

The Zika virus non-structural protein 5 RNA-dependent RNA polymerase (NS5 RdRp) is a vital enzyme for the replication and transcription of the Zika virus RNA genome [2, 4, 12]. As the C-terminal domain of the largest and most conserved non-structural protein in the virus, it catalyzes the synthesis of both positive and negative-sense RNA strands through a de novo initiation mechanism [3, 11, 13]. The enzyme's structure, characterized by a "right-hand" fold with palm, fingers, and thumb subdomains, provides several pockets for small-molecule binding, including the catalytic active site and allosteric regions like the "N-pocket" [13, 16, 17]. Because the RdRp is essential for viral survival and lacks a direct human homolog, it is a primary target for antiviral therapies aimed at treating Zika virus infection and preventing associated complications such as congenital microcephaly and Guillain-Barré syndrome [3, 10, 12, 14]. Current drug discovery efforts focus on nucleoside analogs that cause premature chain termination and non-nucleoside inhibitors that disrupt the enzyme's conformational transitions during RNA synthesis [2, 3, 16].

Other names

Zika virus NS5 RNA-dependent RNA polymeraseZika virus RNA-directed RNA polymeraseZIKV NS5 polymeraseNon-structural protein 5 RNA-dependent RNA polymeraseNS5 RdRp

Nucleoside analog chain termination [2, 3, 12, 16] and allosteric inhibition of the RNA-dependent RNA polymerase activity [2, 3, 10, 13, 16].