Screens for Identifying HIV Fusion Inhibitors

A synthetic peptide, DP-178, representing a discrete region of the HIV fusion protein, gp4l, effectvirus-mediated cell to cell fusion as well as de novo virus infection of T-cells (2). DP-178 has beeselectively to soluble forms of HIV-1 gp41 from which it was derived (4). While DP-178 is promisingtherapeutic, it may exhibit a limited delivery profile characteristic of peptide therapeutics. Theresmall molecule mimic of DP-178, by exploiting the selective binding of this peptide to soluble formsobjectives are to discover and develop a novel class of antivirals for the treatment of HIV infectiodevelop a high through-put biochemical screen based on the binding of DP-178 to gp41 analogs as a finew antiviral leads. Our specific aims are (1) to develop an antibody-based biochemical binding assathrough-put screen; (2) to develop a direct binding biochemical assay suitable as a high through-putcell-based gp41 binding and fusion assay suitable as a high through-put screen; (4) to identify sourscreening.