Ligands that target the HCV-E2 binding site and methods of making and using them. A series of ligand binding sites on the large extracellular loop of the open conformation of CD8 I have been identified. Linking together two or three ligands that bind with low or moderate affinities to different structurally unique sites on a target protein were used to generate small molecule ligand conjugates that exhibit very high affinities to their CD81 targets. Identification and design of groups of compounds that bind to CD8 1 for use as therapeutics for treating patients infected by Hepatitis C vims and other viruses that interact with CD8 I.
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