RNA-directed RNA polymerase (NS7) (RdRp)

The norovirus RNA-dependent RNA polymerase (RdRp), also known as NS7, is a vital enzyme responsible for the replication and transcription of the viral genome (Source 1.2.1, 1.5.3). It catalyzes the synthesis of both genomic and subgenomic positive-sense RNA from a negative-sense RNA intermediate, a process essential for the production of new virions (Source 1.2.4, 1.3.2). RdRp is a primary target for direct-acting antivirals because it lacks a human homolog, potentially reducing off-target effects (Source 1.3.1, 1.6.1). Current therapeutic strategies include nucleoside analogs like favipiravir and ribavirin, which act as chain terminators or induce lethal mutagenesis, and non-nucleoside inhibitors that target allosteric sites (Source 1.2.1, 1.4.1). However, the high mutation rate of noroviruses and the lack of robust cell culture systems present significant challenges for drug development and the prevention of resistance (Source 1.5.3, 1.6.1). Recent research also suggests that RdRp can form liquid-liquid phase-separated condensates that serve as specialized replication factories within host cells (Source 1.2.2, 1.5.1).

Other names

NS7RNA replicaseRNA-dependent RNA polymeraseNorovirus polymerasePolNon-structural protein 7

Nucleoside analogs act as competitive inhibitors that incorporate into the growing RNA chain to cause premature termination or lethal mutagenesis, while non-nucleoside inhibitors bind to allosteric sites to inhibit the initiation or elongation phases of RNA synthesis.