RDRs

RdRs, short for RNA-dependent RNA polymerases, are enzymes that synthesize RNA from an RNA template. They are essential to replication in most RNA viruses and are typically encoded by viral genomes. In cellular biology, RdRps are not part of standard DNA transcription.

Most RdRps contain a conserved catalytic core in the palm domain, with fingers and thumb forming a hand-like structure. The active site includes motifs A through F, especially motif C with a GDD sequence that coordinates divalent metal ions such as Mg2+.

RNA synthesis proceeds in the 5' to 3' direction. Initiation can be de novo or primer-dependent; some viruses use a protein primer (for example VPg in picornaviruses), while others start directly on the template.

RdRps generally have high error rates because they lack proofreading. Some viruses, notably coronaviruses, employ a separate exonuclease (nsp14) to improve fidelity, reducing mutation rates relative to other RNA viruses.

Examples include the RdRps of picornaviruses, flaviviruses, and coronaviruses. The influenza virus uses a multi-subunit RdRp as part of its polymerase complex. The conserved motifs and the GDD active-site motif reflect a shared evolutionary origin among RNA viruses.

RdRps are common antiviral targets. Drugs such as remdesivir and molnupiravir inhibit RdRp function, either by chain termination or inducing mutations. Other nucleoside analogs like ribavirin and favipiravir have broader activity against RNA viruses.