Target intelligence / Profile preview

Hepatitis C virus minus-strand RNA (HCV (-) RNA)

Target
HCV (-) RNA
Molecular classification
Viral RNA, Nucleic acid
01

Overview

The Hepatitis C virus (HCV) minus-strand RNA is a critical replication intermediate produced during the viral life cycle within host hepatocytes. As HCV is a positive-sense single-stranded RNA virus, it must synthesize a complementary negative-strand (minus-strand) RNA to serve as a template for the production of progeny genomic positive-strand RNA (Source: NIH, 2023). This synthesis is catalyzed by the viral RNA-dependent RNA polymerase, NS5B, and occurs within specialized replication complexes associated with the endoplasmic reticulum (Source: Journal of Virology, 2021). Because the minus strand is only present during active viral replication and is not packaged into the virion, its detection is considered a definitive marker of ongoing viral replication (Source: Hepatology, 2020). From a therapeutic perspective, the minus-strand RNA represents a highly specific target for nucleic acid-based interventions, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs). By binding to and promoting the degradation of this template, these agents can effectively halt the production of new viral genomes and proteins, offering a mechanism distinct from current protein-targeting direct-acting antivirals (Source: Nature Biotechnology, 2022). While current standard-of-care treatments primarily utilize small molecule inhibitors of viral proteins, targeting the RNA components remains a significant area of research for overcoming resistance and achieving viral clearance.

Other names
HCV negative-strand RNAHCV antigenomic RNAHepatitis C virus replication intermediate
02

Mechanism of action

Inhibition of viral replication through RNA interference (RNAi) or antisense-mediated degradation of the negative-strand RNA template, preventing the synthesis of progeny positive-strand genomic RNA.

03

Biological functions

Template for RNA-dependent RNA replicationViral genome amplification
04

Disease associations

InfectionChronic Hepatitis CHepatocellular carcinomaLiver cirrhosis
05

Safety considerations

Off-target hybridization with host mRNAInnate immune activation via Toll-like receptors (TLR7/8)Hepatotoxicity related to delivery vehiclesViral escape through sequence mutation
06

Interacting drugs

ALN-HCV (Experimental siRNA)

3 more in the full profile.

07

Biomarkers

Intracellular HCV minus-strand RNA (marker of active replication)

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