Several reports showed that HCV cell entry is a multi-step process.12 Some conserved residues in HCV E2 for CD81 binding were identified and three putative CD81 interacted sites on HCV E2 have also been previously identified.5 ZE2 is partially capable to block HCV E2 from binding to the CD81 receptor and subsequent viral entry and infection of human hepatocytes. Here, CD81 is linked to infection.