Target intelligence / Profile preview

Hepatitis C virus RNA-dependent RNA polymerase (NS5B) (NS5B)

Target
NS5B
Molecular classification
Enzyme, RNA-dependent RNA polymerase, Viral polymerase
01

Overview

Hepatitis C virus RNA-dependent RNA polymerase (NS5B) is a viral enzyme essential for the replication of the hepatitis C virus genome. NS5B catalyzes the polymerization of ribonucleoside triphosphates using the viral positive-sense RNA strand as a template, enabling viral RNA replication via a de novo synthesis mechanism. NS5B is a well-characterized target for direct-acting antivirals due to its indispensable role in the viral life cycle. Several drugs—mainly nucleotide analogs and non-nucleoside allosteric inhibitors—have been developed or approved to inhibit its activity, leading to effective treatments for hepatitis C virus infection. Mutations in the NS5B gene are associated with resistance to specific polymerase inhibitors, which has therapeutic implications for drug selection and resistance testing.

Other names
HCV NS5BHepatitis C virus nonstructural protein 5BNS5B polymerase
02

Mechanism of action

Nucleotide analog inhibitors: act as chain terminators when incorporated into viral RNA (e.g. sofosbuvir) Non-nucleoside inhibitors: bind allosteric sites on the enzyme, impairing its function (e.g. dasabuvir)

03

Biological functions

Viral RNA genome replicationCatalysis of ribonucleoside triphosphate polymerizationDe novo RNA synthesis
04

Disease associations

Infection (Hepatitis C virus infection)Chronic hepatitisLiver cirrhosisHepatocellular carcinoma (as a consequence of chronic infection)
05

Safety considerations

Viral resistance due to mutations in NS5B (notably S282T and others)General safety profiles relate to individual antivirals targeting NS5B rather than the target itself
06

Interacting drugs

Sofosbuvir

6 more in the full profile.

07

Biomarkers

Quantitative HCV RNA levels (as a surrogate for NS5B activity and treatment efficacy)Amino acid substitutions in NS5B (resistance testing; e.g., S282T mutation)

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