The green tea polyphenol epigallocatechin-3-gallate (EGCG) inhibits hepatitis C virus (HCV) entry.
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 non-structural proteins required for RNA replication. Individuals undergoing orthotopic liver transplantation face rapid and 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), epicatechingallate (ECG) and epicatechin (EC), have been previously found to exert antiviral and anti-oncogenic properties. EGCG had no effect on HCV RNA replication, assembly or release of progeny virions. However, it potently inhibited 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 extra-cellular virions and cell-to-cell spread were blocked. Pretreatment of cells with EGCG before HCV inoculation did not reduce HCV infection while 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. Conclusion: 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. (HEPATOLOGY 2011.).
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