4 Therefore, combinations of drugs targeting different steps of the viral life cycle, including virus entry, would likely improve viral response rates and therapeutic success. HCV is a small enveloped virus with a positive stranded RNA genome belonging to the Hepacivirus genus in the Flaviviridae family. 5 Its genome encodes two envelope glycoproteins,
E1 and E2, which play a key role in virus RXDX-106 order entry into the hepatocyte. HCV entry is a complex, multistep process involving sequential interactions with several cell-surface proteins. 6 The virus relies on glycosaminoglycans and perhaps on low-density lipoprotein receptor to attach to cells. Furthermore, four specific entry factors— scavenger receptor class B type 1, tetraspanin cluster of differentiation (CD)81, claudin-1, and occludin— are sequentially involved after initial virus binding. Finally, HCV enters cells via clathrin-mediated endocytosis. 7 The viral
particle also has the peculiar selleck chemicals feature of being associated with low- or very-low-density lipoproteins. 7 Importantly, two modes of infection have been observed in vitro: either cell-free or cell-to-cell transmission, with the latter being refractory to neutralization by anti-E2 antibodies, thus representing an alternative mode of transmission, which may be important in vivo. 8 Green tea has a potential to effect a variety of human diseases, in particular, cancers. 9 Most of the properties of green tea are mediated by (−)-epigallocatechin-3-gallate (EGCG), the most abundant polyphenol catechin present in green tea extracts. EGCG administration is safe in healthy individuals.
10 EGCG also displays some antiviral activity against human immunodeficiency virus (HIV), IKBKE human herpes simplex virus (HSV), and influenza virus. 11-13 In all cases, EGCG was shown to inhibit entry, either by targeting cellular proteins, CD4 receptor for HIV, 11 and nuclear factor erythroid 2–related factor 2 for influenza, 14 or by direct action on the particle for HSV and influenza. 11, 13 Furthermore, EGCG was shown to increase lipid-droplet formation and to impair very-low-density lipoprotein secretion in hepatocytes. 15 Thus, because of the link between lipid metabolism and HCV life cycle, we hypothesized that this molecule might interfere with HCV. Here, we investigated the potential antiviral effect of EGCG on HCV. Importantly, our data show that EGCG is a new anti-HCV agent that blocks an early step of the entry process, the attachment step, probably by targeting HCV particle.