Different anti-HCV profiles of statins and their potential for combination therapy with interferon
- PMID: 16799963
- DOI: 10.1002/hep.21232
Different anti-HCV profiles of statins and their potential for combination therapy with interferon
Abstract
We recently developed a genome-length hepatitis C virus (HCV) RNA replication system (OR6) with luciferase as a reporter. The OR6 assay system has enabled prompt and precise quantification of HCV RNA replication. Pegylated interferon (IFN) and ribavirin combination therapy is the world standard for chronic hepatitis C, but its effectiveness is limited to about 55% of patients. Newer therapeutic approaches are needed. In the present study, we used the OR6 assay system to evaluate the anti-HCV activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, called statins, and their effects in combination with IFN-alpha. Five types of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) were examined for their anti-HCV activities. Fluvastatin exhibited the strongest anti-HCV activity (IC50: 0.9 micromol/L), whereas atorvastatin and simvastatin showed moderate inhibitory effects. However, lovastatin, reported recently as an inhibitor of HCV replication, was shown to exhibit the weakest anti-HCV activity. The anti-HCV activities of statins were reversed by the addition of mevalonate or geranylgeraniol. Surprisingly, however, pravastatin exhibited no anti-HCV activity, although it worked as an inhibitor for HMG-CoA reductase. The combination of IFN and the statins (except for pravastatin) exhibited strong inhibitory effects on HCV RNA replication. In combination with IFN, fluvastatin also exhibited a synergistic inhibitory effect. In conclusion, statins, especially fluvastatin, could be potentially useful as new anti-HCV reagents in combination with IFN.
Comment in
-
Statins and HCV: a complex issue.Hepatology. 2007 Jan;45(1):257. doi: 10.1002/hep.21506. Hepatology. 2007. PMID: 17187410 No abstract available.
Similar articles
-
Combination of fluvastatin with pegylated interferon/ribavirin therapy reduces viral relapse in chronic hepatitis C infected with HCV genotype 1b.J Gastroenterol Hepatol. 2013 Jan;28(1):51-6. doi: 10.1111/j.1440-1746.2012.07267.x. J Gastroenterol Hepatol. 2013. PMID: 22989264 Clinical Trial.
-
Does fluvastatin favour HCV replication in vivo? A pilot study on HIV-HCV coinfected patients.J Viral Hepat. 2009 Jul;16(7):479-84. doi: 10.1111/j.1365-2893.2009.01104.x. Epub 2009 Feb 8. J Viral Hepat. 2009. PMID: 19215577 Clinical Trial.
-
Life style-related diseases of the digestive system: cell culture system for the screening of anti-hepatitis C virus (HCV) reagents: suppression of HCV replication by statins and synergistic action with interferon.J Pharmacol Sci. 2007 Oct;105(2):145-50. doi: 10.1254/jphs.fm0070050. Epub 2007 Oct 6. J Pharmacol Sci. 2007. PMID: 17928739 Review.
-
Chronic hepatitis C virus infection in renal transplant: treatment and outcome.Clin Transplant. 2006 Nov-Dec;20(6):677-83. doi: 10.1111/j.1399-0012.2006.00534.x. Clin Transplant. 2006. PMID: 17100715
-
Selective inhibitors of hepatitis C virus replication.Antiviral Res. 2006 Sep;71(2-3):363-71. doi: 10.1016/j.antiviral.2006.06.006. Epub 2006 Jun 23. Antiviral Res. 2006. PMID: 16843538 Review.
Cited by
-
A Dual Pharmacological Strategy against COVID-19: The Therapeutic Potential of Metformin and Atorvastatin.Microorganisms. 2024 Feb 13;12(2):383. doi: 10.3390/microorganisms12020383. Microorganisms. 2024. PMID: 38399787 Free PMC article. Review.
-
Hepatitis C Virus (HCV)-Ribonucleic Acid (RNA) As a Biomarker for Lymphoid Malignancy with HCV Infection.Cancers (Basel). 2023 May 21;15(10):2852. doi: 10.3390/cancers15102852. Cancers (Basel). 2023. PMID: 37345190 Free PMC article. Review.
-
Preparing for the next viral threat with broad-spectrum antivirals.J Clin Invest. 2023 Jun 1;133(11):e170236. doi: 10.1172/JCI170236. J Clin Invest. 2023. PMID: 37259914 Free PMC article. Review.
-
Efficacy and safety of metabolic interventions for the treatment of severe COVID-19: in vitro, observational, and non-randomized open-label interventional study.Elife. 2023 Jan 27;12:e79946. doi: 10.7554/eLife.79946. Elife. 2023. PMID: 36705566 Free PMC article. Clinical Trial.
-
Statin Use Reduces the Risk of Hepatocellular Carcinoma: An Updated Meta-Analysis and Systematic Review.Cureus. 2022 Jul 19;14(7):e27032. doi: 10.7759/cureus.27032. eCollection 2022 Jul. Cureus. 2022. PMID: 35989795 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical