RDR

RdR stands for RNA-dependent RNA polymerase, an enzyme that copies RNA from an RNA template. It is a central component of the replication machinery for RNA viruses, enabling genome amplification without a DNA intermediate. While RdRp is the more commonly used abbreviation in modern literature, some sources still use RdR.

RdR enzymes catalyze the synthesis of RNA in a template-directed manner, typically using nucleoside triphosphates and divalent metal ions such as magnesium or manganese. Structurally, many RdRps resemble a right-handed palm–fingers–thumb arrangement. The catalytic center contains conserved motifs, often including an aspartate-rich motif such as the DD or GDD triad in motif C, which coordinates metal ions for phosphodiester bond formation. Many RdRps lack proofreading exonuclease activity, contributing to the relatively high mutation rates observed in RNA viruses; some lineages, however, have accessory activities that confer limited proofreading.

RdRs are encoded by nearly all RNA viruses, including positive-sense viruses like picornaviruses, flaviviruses, and coronaviruses; negative-sense and double-stranded RNA viruses also rely on RdRps for replication. In many viruses, the RdRp is part of a larger replication complex that includes auxiliary proteins and membrane-associated components to coordinate RNA synthesis, processing, and capping.

Because RdRps are essential for viral replication and absent in host DNA-directed polymerases, they are important antiviral targets. Therapeutic strategies include nucleotide analogs that terminate RNA synthesis and non-nucleoside inhibitors that bind to the active site or allosteric regions. Resistance can arise through mutations in conserved motifs or in nearby replication proteins, complicating treatment.

Note: the term RdR is sometimes used interchangeably with RdRp, but readers should consider context to avoid ambiguity with other polymerases.