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Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells
  1. Anggakusuma1,
  2. Che C Colpitts2,
  3. Luis M Schang2,
  4. Heni Rachmawati3,
  5. Anne Frentzen1,
  6. Stephanie Pfaender1,
  7. Patrick Behrendt1,5,
  8. Richard J P Brown1,
  9. Dorothea Bankwitz1,
  10. Joerg Steinmann4,
  11. Michael Ott5,6,
  12. Philip Meuleman7,
  13. Charles M Rice8,
  14. Alexander Ploss8,9,
  15. Thomas Pietschmann1,
  16. Eike Steinmann1
  1. 1Institute of Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany
  2. 2Departments of Biochemistry and Medical Microbiology and Immunology, Li Ka Shing Insitute of Virology, University of Alberta, Edmonton, Alberta, Canada
  3. 3School of Pharmacy, Institut Teknologi Bandung, Bandung, Indonesia
  4. 4Institute of Medical Microbiology, University Hospital Essen, Essen, Germany
  5. 5Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany
  6. 6Translational Research Group, Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany
  7. 7Center for Vaccinology, Ghent University, Ghent University hospital, Ghent, Belgium
  8. 8Laboratory of Virology and Infectious Diseases, Center for the Study of Hepatitis C, The Rockefeller University, New York, New York, USA
  9. 9Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA
  1. Correspondence to Dr Eike Steinmann, Institute of Experimental Virology, Twincore Center for Experimental and Clinical Infection Research (a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI)), Feodor-Lynen-Straße 7-9, Hannover 30625, Germany; eike.steinmann{at}twincore.de

Abstract

Objective Hepatitis C virus (HCV) infection causes severe liver disease and affects more than 160 million individuals worldwide. People undergoing liver organ transplantation face universal re-infection of the graft. Therefore, affordable antiviral strategies targeting the early stages of infection are urgently needed to prevent the recurrence of HCV infection. The aim of the study was to determine the potency of turmeric curcumin as an HCV entry inhibitor.

Design The antiviral activity of curcumin and its derivatives was evaluated using HCV pseudo-particles (HCVpp) and cell-culture-derived HCV (HCVcc) in hepatoma cell lines and primary human hepatocytes. The mechanism of action was dissected using R18-labelled virions and a membrane fluidity assay.

Results Curcumin treatment had no effect on HCV RNA replication or viral assembly/release. However, co-incubation of HCV with curcumin potently inhibited entry of all major HCV genotypes. Similar antiviral activities were also exerted by other curcumin derivatives but not by tetrahydrocurcumin, suggesting the importance of α,β-unsaturated ketone groups for the antiviral activity. Expression levels of known HCV receptors were unaltered, while pretreating the virus with the compound reduced viral infectivity without viral lysis. Membrane fluidity experiments indicated that curcumin affected the fluidity of the HCV envelope resulting in impairment of viral binding and fusion. Curcumin has also been found to inhibit cell-to-cell transmission and to be effective in combination with other antiviral agents.

Conclusions Turmeric curcumin inhibits HCV entry independently of the genotype and in primary human hepatocytes by affecting membrane fluidity thereby impairing virus binding and fusion.

  • Antiviral Therapy
  • Chronic Viral Hepatitis
  • Drug Development
  • HCV

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