fax: 32-16-337340
Viral Hepatitis
You have full text access to this OnlineOpen article
Statins potentiate the in vitro anti-hepatitis C virus activity of selective hepatitis C virus inhibitors and delay or prevent resistance development†
Article first published online: 18 FEB 2009
DOI: 10.1002/hep.22916
Copyright © 2009 American Association for the Study of Liver Diseases
Additional Information
How to Cite
Delang, L., Paeshuyse, J., Vliegen, I., Leyssen, P., Obeid, S., Durantel, D., Zoulim, F., Op de Beeck, A. and Neyts, J. (2009), Statins potentiate the in vitro anti-hepatitis C virus activity of selective hepatitis C virus inhibitors and delay or prevent resistance development. Hepatology, 50: 6–16. doi: 10.1002/hep.22916
- †
Potential conflict of interest: Nothing to report.
Publication History
- Issue published online: 23 JUN 2009
- Article first published online: 18 FEB 2009
- Accepted manuscript online: 18 FEB 2009 12:00AM EST
- Manuscript Accepted: 11 FEB 2009
- Manuscript Received: 12 SEP 2008
Funded by
- Fonds voor Wetenschappelijk Onderzoek (FWO) Vlaanderen and FWO
- VIRGIL
- European Network of Excellence on Antiviral Drug Resistance (Priority 1 Life Sciences, Genomics and Biotechnology). Grant Number: LSHM-CT-2004-503359
- Fonds National de la Recherche Scientifique. Grant Number: No.3.4.545.06.F
References
- 1, , , . Clinical consequences of hepatitis C virus infection. Rev Med Virol 2003; 13: 57–68.Direct Link:
- 2, . Old and emerging therapies in chronic hepatitis C: an update. J Viral Hepat 2008; 15: 2–11.
- 3, , , , , , et al. Antiviral efficacy of NS3-serine protease inhibitor BILN-2061 in patients with chronic genotype 2 and 3 hepatitis C. HEPATOLOGY 2005; 41: 832–835.Direct Link:
- 4. Selective inhibitors of hepatitis C virus replication. Antiviral Res 2006; 71: 363–371.
- 5, , , , , , et al. Efficacy and safety of valopicitabine in combination with pegylated interferon-α (PEG IFN) and ribavirin (RBV) in patients with chronic hepatitis C. HEPATOLOGY 2007; 46(Suppl): LB15.
- 6. Non-nucleoside inhibitors of the HCV NS5B polymerase: progress in the discovery and development of novel agents for the treatment of HCV infections. Curr Opin Investig Drugs 2007; 8: 614–634.
- 7, , , , , , et al. The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus. HEPATOLOGY 2008; 47: 817–826.Direct Link:
- 8, . Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc Natl Acad Sci U S A 2005; 102: 2561–2566.
- 9. Reliance of host cholesterol metabolic pathways for the life cycle of hepatitis C virus. PLoS Pathog 2007; 3: e108.
- 10, , , , , , et al. Statin-induced inhibition of HIV-1 release from latently infected U1 cells reveals a critical role for protein prenylation in HIV-1 replication. Microbes Infect 2008; 1–10.
- 11, , , , , , et al. Statins inhibit HIV-1 infection by down-regulating Rho activity. J Exp Med 2004; 200: 541–547.
- 12, . Statin compounds reduce human immunodeficiency virus type 1 replication by preventing the interaction between virion-associated host intercellular adhesion molecule 1 and its natural cell surface ligand LFA-1. J Virol 2004; 78: 12062–12065.
- 13, , . Role of simvastatin and methyl-beta-cyclodextrin on inhibition of poliovirus infection. Biochem Biophys Res Commun 2006; 347: 51–59.
- 14, , , , , , et al. Hydroxymethyl-glutaryl coenzyme a reductase inhibition limits cytomegalovirus infection in human endothelial cells. Circulation 2004; 109: 532–536.
- 15, . Antiviral activity of lovastatin against respiratory syncytial virus in vivo and in vitro. Antimicrob Agents Chemother 2001; 45: 1231–1237.
- 16, , , , , . Different anti-HCV profiles of statins and their potential for combination therapy with interferon. HEPATOLOGY 2006; 44: 117–125.Direct Link:
- 17, , , , , , et al. Targeting lipid metabolism in the treatment of hepatitis C virus infection. J Infect Dis 2008; 197: 361–370.
- 18, , , , , Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Natl Acad Sci U S A 2003; 100: 15865–15870.
- 19, , , , , , et al. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mol Cell 2005; 18: 425–434.
- 20, , , , , . Analysis of HCV NS5B genetic variants following monotherapy with HCV-796, a nonnucleoside polymerase inhibitor, in treatment-naïve HCV-infected patients. HEPATOLOGY 2006; 44: 607A–608A.
- 21, , , , , , et al. Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology 2007; 132: 1767–1777.
- 22, , , , , . Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 1999; 285: 110–113.
- 23, , , , , , et al. A replicon-based bioassay for the measurement of interferons in patients with chronic hepatitis C. J Virol Methods 2003; 110: 201–209.
- 24, , , , , , et al. Comparative in vitro anti-hepatitis C virus activities of a selected series of polymerase, protease, and helicase inhibitors. Antimicrob Agents Chemother 2008; 52: 3433–3437.
- 25, , , , , , et al. The non-immunosuppressive cyclosporin DEBIO-025 is a potent inhibitor of hepatitis C virus replication in vitro. HEPATOLOGY 2006; 43: 761–770.Direct Link:
- 26, , , , , , et al. Robust production of infectious viral particles in Huh-7 cells by introducing mutations in hepatitis C virus structural proteins. J Gen Virol 2007; 88: 2495–2503.
- 27, , , , , , et al. Differential antiviral activity of derivatized dextrans. Biochem Pharmacol 1995; 50: 743–751.
- 28, A three-dimensional model to analyze drug-drug interactions. Antiviral Res 1990; 14: 181–205.
- 29, . 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; 105: 145–150.
- 30, , , , , , et al. Molecular mechanism of hepatitis C virus replicon variants with reduced susceptibility to a benzofuran inhibitor, HCV-796. Antimicrob Agents Chemother 2008; 52: 3327–3338.
- 31, , . The novel immunosuppressive agent mycophenolate mofetil markedly potentiates the antiherpesvirus activities of acyclovir, ganciclovir, and penciclovir in vitro and in vivo. Antimicrob Agents Chemother 1998; 42: 216–222.
- 32, . The human liver-uPA-SCID mouse: a model for the evaluation of antiviral compounds against HBV and HCV. Antiviral Res 2008; 80: 231–238.
- 33, , , . Antiviral drugs that target cellular proteins may play major roles in combating HIV resistance. Curr Pharm Des 2004; 10: 4081–4101.
- 34, , , . Atorvastatin does not exhibit antiviral activity against HCV at conventional doses: a pilot clinical trial. HEPATOLOGY 2007; 45: 895–898.Direct Link:
- 35, , , , , , et al. A pilot study to assess the impact of rosuvastatin therapy on HCV RNA and lipid fractions in chronic hepatitis c patients. Gastroenterology 2007; 132: A741.
- 36, , , , , , et al. Fluvastatin inhibits hepatitis C replication in humans. Am J Gastroenterol 2008; 103: 1383–1389.Direct Link:
- 37, , , . Modelling how ribavirin improves interferon response rates in hepatitis C virus infection. Nature 2004; 432: 922–924.
- 38, , . Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation 2004; 109(23 Suppl 1 ): III50–III57.
- 39, , , . Disposition of fluvastatin, an inhibitor of HMG-COA reductase, in mouse, rat, dog, and monkey. Biopharm Drug Dispos 1990; 11: 519–531.Direct Link:
- 40, , , , , , et al. Liver-specific distribution of rosuvastatin in rats: comparison with pravastatin and simvastatin. Drug Metab Dispos 2002; 30: 1158–1163.
- 41, . HPLC determination of lovastatin in rat tissue. Chromatographia 2007; 66: 487–491.
- 42. The safety of statins in clinical practice. Lancet 2007; 370: 1781–1790.

1527-3350/asset/olbannerleft.gif?v=1&s=4b2409f9534ed500d3c8da1940a23842e2b9932d)
1527-3350/asset/olbannerright.gif?v=1&s=141b9a8485298533c3e2016e937b0404f7d933e1)
