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Hepatology International

, Volume 11, Issue 5, pp 440–445 | Cite as

A cinnamon-derived procyanidin type A compound inhibits hepatitis C virus cell entry

  • Catherine Fauvelle
  • Melanie Lambotin
  • Laura Heydmann
  • Ekambaranellore Prakash
  • Sunil Bhaskaran
  • Mohan Vishwaraman
  • Thomas F. Baumert
  • Christiane Moog
Original Article

Abstract

Background and aims

Chronic hepatitis C virus (HCV) infection is a major cause of liver disease worldwide. Although direct-acting antivirals can cure the large majority of treated patients, important limitations remain, including treatment failure and high costs precluding access to therapy in resource-limited settings. We report herein the anti-HCV effects of IND02, a procyanidin type A molecule, isolated and characterized from cinnamon.

Methods and results

Using cellculture-derived HCV (HCVcc), HCV pseudoparticles (HCVpp), and subgenomic replicons, we demonstrated that IND02 markedly and dose-dependently inhibited HCV cell entry. Kinetic assays demonstrated that IND02 inhibits HCV entry most likely at a postbinding step. Experiments performed using primary human hepatocytes confirmed inhibition of HCV entry by IND02, demonstrating the functional impact in the most physiological cell-based system for studying HCV–host interactions.

Conclusions

The natural compound IND02 exhibits potent HCV cell entry inhibition and provides a novel perspective for development of a low-cost antiviral for treatment of HCV infection.

Keywords

Antiviral IND02 Hepatitis C Infection Liver 

Abbreviations

HCV

Hepatitis C virus

LT

Liver transplantation

EGCG

(−)-Epigallocatechin-3-gallate

HCVcc

Cellculture-derived HCV

HCVpp

HCV pseudoparticles

VSV

Vesicular stomatitis virus

TCID50

50 % tissue culture infective dose

PHH

Primary human hepatocytes

EC50

50 % effective concentration

nAbs

Neutralizing antibodies

Notes

Acknowledgements

The authors thank F. Chisari (The Scripps Research Institute, La Jolla, CA) for the gift of Huh7.5.1 cells, T. Wakita (Department of Virology II, National Institutes of Health, Tokyo, Japan), C. M. Rice (Rockefeller University, New York, NY) for providing HCV strain JFH1, and R. Bartenschlager (University of Heidelberg, Heidelberg, Germany) for HCV strain Luc-Jc1 and VL:JFH1. The authors thank P. Pessaux (Strasbourg University Hospitals) for liver resection to isolate PHH. The authors thank Eric Soulier for technical assistance in PHH experiments and HCV RT-PCR, and Dr. Luzia Mayr and Dr. Mirjam Zeisel for helpful discussions and support in manuscript editing.

Author contributions

M.L., C.F., C.M., and T.F.B. wrote the manuscript. M.L., C.F., E.P., C.M., and T.F.B. designed experiments. M.L., C.F., and L.H. performed experiments. M.L., C.F., L.H., C.M., and T.F.B. analyzed data. E.P. and B.S. provided reagents. M.V. isolated and purified IND02. C.M. and T.F.B. directed the project.

Compliance with ethical standards

Conflict of interest

The authors disclose the following: E. Prakash, S. Bhaskaran, and M. Vishwaraman are employed by Indus Biotech. Authors C. Fauvelle, M. Lambotin, L. Heydmann, T. F. Baumert, and C. Moog declare no conflicts. Part of the research was funded by Indus Biotech Pvt Ltd, but this sponsor had no impact on experimental design or data analyses.

Ethical approval

Liver tissue from patients undergoing surgical resection for isolation of human hepatocytes was obtained with informed consent from all patients. The protocol was approved by the Ethics Committee of the University of Strasbourg Hospitals (CPP 10-17).

Funding information

This work was supported by Dormeur Investment Service Ltd. and Indus Biotech Pvt ltd. M.L. was supported by the European Community’s Seventh Framework Programme (FP7/2007-2013; EuroNeut41).

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Copyright information

© Asian Pacific Association for the Study of the Liver 2017

Authors and Affiliations

  • Catherine Fauvelle
    • 1
    • 2
  • Melanie Lambotin
    • 1
    • 2
    • 3
  • Laura Heydmann
    • 1
    • 2
  • Ekambaranellore Prakash
    • 4
  • Sunil Bhaskaran
    • 4
  • Mohan Vishwaraman
    • 4
  • Thomas F. Baumert
    • 1
    • 2
    • 5
  • Christiane Moog
    • 1
    • 2
    • 6
  1. 1.Inserm, U1110, Institut de Recherche sur les Maladies Virales et HépatiquesStrasbourgFrance
  2. 2.Université de StrasbourgStrasbourgFrance
  3. 3.Association ORACLE, Centre d’Oncologie de GentillyNancyFrance
  4. 4.Indus Biotech Pvt LtdPuneIndia
  5. 5.Institut Hospitalo-Universitaire, Pôle Hépato-digestifHôpitaux Universitaires de StrasbourgStrasbourgFrance
  6. 6.Inserm, U1109, Fédération de Médecine Translationnelle (FMTS)StrasbourgFrance

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