CD81 and infection: By targeting sites containing amino acid residues identified by others to participate in CD81 binding and CD81-dependent processes that impact HCV infectivity, a small molecule was identified that not only blocks E2 binding to CD81 and the cell-free entry process, but it is also effective in blocking the cell-to-cell transmission of HCV – the predominant mechanism of transmission that contributes to the persistence of infections [41] but for which the precise mechanism needs to be defined.