title: The green tea polyphenol, epigallocatechin-3-gallate, inhibits hepatitis C virus entry.
abstract: Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Current antiviral therapy fails to clear infection in a substantial proportion of cases. Drug development is focused on nonstructural proteins required for RNA replication. Individuals undergoing orthotopic liver transplantation face rapid, universal reinfection of the graft. Therefore, antiviral strategies targeting the early stages of infection are urgently needed for the prevention of HCV infection. In this study, we identified the polyphenol, epigallocatechin-3-gallate (EGCG), as an inhibitor of HCV entry. Green tea catechins, such as EGCG and its derivatives, epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC), have been previously found to exert antiviral and antioncogenic properties. EGCG had no effect on HCV RNA replication, assembly, or release of progeny virions. However, it potently inhibited Cell-culture-derived HCV (HCVcc) entry into hepatoma cell lines as well as primary human hepatocytes. The effect was independent of the HCV genotype, and both infection of cells by extracellular virions and cell-to-cell spread were blocked. Pretreatment of cells with EGCG before HCV inoculation did not reduce HCV infection, whereas the application of EGCG during inoculation strongly inhibited HCV infectivity. Moreover, treatment with EGCG directly during inoculation strongly inhibited HCV infectivity. Expression levels of all known HCV (co-)receptors were unaltered by EGCG. Finally, we showed that EGCG inhibits viral attachment to the cell, thus disrupting the initial step of HCV cell entry.
  
  
  CONCLUSIONS
  The green tea molecule, EGCG, potently inhibits HCV entry and could be part of an antiviral strategy aimed at the prevention of HCV reinfection after liver transplantation.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ciesek
authors.forename: Thomas
authors.initials: T
authors.lastname: von Hahn
authors.forename: Che C
authors.initials: CC
authors.lastname: Colpitts
authors.forename: Luis M
authors.initials: LM
authors.lastname: Schang
authors.forename: Martina
authors.initials: M
authors.lastname: Friesland
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinmann
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Michael
authors.initials: M
authors.lastname: Ott
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Philip
authors.initials: P
authors.lastname: Meuleman
authors.forename: Thomas
authors.initials: T
authors.lastname: Pietschmann
authors.forename: Eike
authors.initials: E
authors.lastname: Steinmann
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006526:Hepatitis C / Q000517:prevention & control*; D006801:Humans; D013662:Tea / Q000737:chemistry; D053585:Virus Attachment / Q000187:drug effects*; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate