Target intelligence / Profile preview

RNA-dependent RNA Polymerase (RdRp)

Target
RdRp
Molecular classification
Enzyme, Polymerase
01

Overview

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.

Other names
RNA replicase
02

Mechanism of action

Inhibition of RNA-dependent RNA polymerase activity, preventing viral genome replication and transcription.

03

Biological functions

Viral genome replicationViral transcriptionRNA synthesisPost-transcriptional gene silencing (in some eukaryotes)
04

Disease associations

Infection
05

Safety considerations

Potential for off-target effectsDevelopment of drug resistance
06

Interacting drugs

Inhibitors developed against hepatitis C virus

1 more in the full profile.

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