ArticleScientific reports2016
Efficient Suppression of Hepatitis C Virus Replication by Combination Treatment with miR-122 Antagonism and Direct-acting Antivirals in Cell Culture Systems.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- X-inactive specific transcript (XIST) can determine sex differences in cardiovascular drug responses: focus on RNA therapeutics.Frontiers in pharmacology · 2025Article
- Transcriptional Inhibition of MicroRNA miR-122 by Small Molecules Reduces Hepatitis C Virus Replication in Liver Cells.Journal of medicinal chemistry · 2022Article
- MicroRNA-122 Regulation of HCV Infections: Insights from Studies of miR-122-Independent Replication.Pathogens (Basel, Switzerland) · 2022Review
- Review
- Hepatocellular carcinoma, hepatitis C virus infection and miRNA involvement: Perspectives for new therapeutic approaches.World journal of gastroenterology · 2022Review
- MicroRNA 122 Affects both the Initiation and the Maintenance of Hepatitis C Virus Infections.Journal of virology · 2022Article
- Role of Different Types of miRNAs in Some Cardiovascular Diseases and Therapy-Based miRNA Strategies: A Mini Review.BioMed research international · 2022Review
- Review
- The powerful world of antisense oligonucleotides: From bench to bedside.Wiley interdisciplinary reviews. RNA · 2020Review
- The Role of the Liver-Specific microRNA, miRNA-122 in the HCV Replication Cycle.International journal of molecular sciences · 2020Review
- Depletion of MicroRNA-373 Represses the Replication of Hepatitis C Virus via Activation of Type 1 Interferon Response by Targeting IRF5.Yonsei medical journal · 2018Article
- Differentiation in stem/progenitor cells along fetal or adult hepatic stages requires transcriptional regulators independently of oscillations in microRNA expression.Experimental cell research · 2018Article
- Unexpected Replication Boost by Simeprevir for Simeprevir-Resistant Variants in Genotype 1a Hepatitis C Virus.Antimicrobial agents and chemotherapy · 2018Article
- Host-targeting therapies for hepatitis C virus infection: current developments and future applications.Therapeutic advances in gastroenterology · 2018Review
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Direct-acting antivirals (DAAs) against Hepatitis C virus (HCV) show effective antiviral activity with few side effects. However, the selection of DAA-resistance mutants is a growing problem that needs to be resolved. In contrast, miR-122 antagonism shows extensive antiviral effects among all HCV genotypes and a high barrier to drug resistance. In the present study, we evaluated three DAAs (simeprevir, daclatasvir, and sofosbuvir) in combination with anti-miR-122 treatment against HCV genotype 1a in cell cultures. We found that combination treatments with anti-miR-122 and a DAA had additive or synergistic antiviral effects. The EC50 values of simeprevir in simeprevir-resistant mutants were significantly decreased by combining simeprevir with anti-miR-122. A similar reduction in EC50 in daclatasvir-resistant mutants was achieved by combining daclatasvir with anti-miR-122. Combination treatment in HCV-replicating cells with DAA and anti-miR-122 sharply reduced HCV RNA amounts. Conversely, DAA single treatment with simeprevir or daclatasvir reduced HCV RNA levels initially, but the levels later rebounded. DAA-resistant mutants were less frequently observed in combination treatments than in DAA single treatments. In summary, the addition of miR-122 antagonism to DAA single treatments had additive or synergistic antiviral effects and helped to efficiently suppress HCV replication and the emergence of DAA-resistant mutants.
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