New translational research on novel drugs for hepatitis C virus 1b infection by using a replicon system and human induced pluripotent stem cells

Authors

  • Hisashi Moriguchi,

    1. Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
    2. Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA
    3. Department of Analytical Health Science, Graduate School of Health Sciences, Tokyo Medical and Dental University, Tokyo, Japan
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  • Raymond T Chung,

    1. Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA
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  • Chifumi Sato

    1. Department of Analytical Health Science, Graduate School of Health Sciences, Tokyo Medical and Dental University, Tokyo, Japan
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  • Potential conflict of interest: Nothing to report.

New Translational Research on Novel Drugs for Hepatitis C Virus 1b Infection by Using a Replicon System and Human Induced Pluripotent Stem Cells

To the Editor:

We read with interest the article by Delang et al.1 They showed excellent antiviral effects for the combination of hepatitis C virus (HCV) polymerase or protease inhibitors with mevastatin or simvastatin in vitro.1 However, they did not use atorvastatin and pitavastatin in their study.1

According to our replicon system,2 atorvastatin or pitavastatin was more effective for HCV-1b infection among monotherapy of statins (Fig. 1). This result is also supported by an experimental study.3 For example, median effective concentration (EC50) value was 2.16, 1.57, 1.39, 0.90, and 0.45 μM in lovastatin, simvastatin, atorvastatin, fluvastatin, and pitavastatin, respectively.3 Therefore, pitavastatin possessed the strongest anti-HCV activity among the statins tested.3 Considering these facts, antiviral effects in HCV-1b infection for the combination of HCV polymerase or protease inhibitors with pitavastatin should be also considered in vitro.

Figure 1.

Efficacy of several drugs against HCV infection among monotherapy of statins. Vertical axis; Relative luciferase activity (% of control) horizontal axis; statins (μM), IFN (U/mL) ATV, atorvastatin; FLV, fluvastatin; IFN, interferon; PTV, pitavastatin; SMV, simvastatin. MTS; 5-(3-carboxymethoxyphenyl)-2-(4,5-dimethylthiazoly)-3-(4-sulfophenyl)tetra-zolium, inner salt).

In addition, the toxicities for these combination therapies should be evaluated appropriately. As for this point, human induced pluripotent stem cells (iPSCs) can be efficiently induced to differentiate into hepatocyte-like cells.4 This suggest that human iPSCs derived from patients with HCV-1b infection can differentiate into hepatocyte-like cells. By using the patient-specific hepatocyte-like cells, the patient-specific toxicities for the abovementioned combination therapies for HCV-1b infection could be evaluated in the near future.

In conclusion, we describe a method to effectively progress the translational research on novel combination therapies for HCV-1b infection. Acknowledgment: We are grateful to Dr. Naoya Sakamoto and other members of our laboratories for technical support. Furthermore, we are also grateful to Ms. Satoko Iioka for helpful discussions.

Acknowledgements

We are grateful to Dr. Naoya Sakamoto and other members of our laboratories for technical support. Furthermore, we are also grateful to Ms. Satoko Iioka for helpful discussions.

Hisashi Moriguchi* † ‡, Raymond T Chung†, Chifumi Sato‡, * Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan, † Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, ‡ Department of Analytical Health Science, Graduate School of Health Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

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