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RNA-dependent RNA polymerase (RdRp), also known as RNA replicase, is an enzyme that catalyzes the synthesis of an RNA strand complementary to a given RNA template. It is essential for the replication and transcription of most viruses with single-stranded or double-stranded RNA genomes that lack a DNA stage. RdRp is an attractive target for antiviral drug development because it is indispensable for replication/transcription in many pathogenic viruses but absent from host cells lacking cytoplasmic replicating RNAs. The enzyme's structure resembles a cupped right hand, with fingers, palm (containing catalytic residues), and thumb subdomains. The catalytic mechanism involves binding of an NTP substrate, deprotonation of the primer's 3' hydroxyl group, and nucleophilic attack on the α-phosphate of the incoming NTP, forming a phosphodiester bond and releasing pyrophosphate. Priming strategies vary among viruses, including primer-independent initiation, use of protein primers, and cap-snatching mechanisms.
Inhibition of RNA-dependent RNA polymerase activity, preventing viral genome replication and transcription.
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