SBIR-STTR Award

Viral Therapeutics proposes to develop an assay system to enable drug discovery for a class of compounds that would block viral fusion and entry by targeting a novel specific receptor interaction. The company will use proprietary recombinant proteins and peptides derived from HIV gp41 sequences to use as ligands for receptor binding. Two of the recombinant proteins produced in P. pastoris have been produced and are available to the research community through NEN Dupont, while at least one other recombinant will be developed. The cell-based screening assay will be developed using a cell capture system provided by NEN Dupont that is currently under review by the FDA. The assay system employ's a signal amplification cascade using antibody against a FITC labelled ligand to which HRP is conjugated. Ten thousand cells per microtiter well can be reproducibly bound and since the number of fusion receptor molecules per cell is comparable to the number of CD4 molecules it is anticipated that adequate sensitivity will be achieved. Alternative approaches are proposed. Ligand binding characteristics and competitive inhibition in the Fusion Drug assay will be determined. Extracts from plants and other sources will be used to test the assay system's limits of sensitivity to concentrations of known ligand inhibitors under expected field conditions.Proposed commercial application:A successful HIV fusion assay targeting a specific interaction would be an invaluable tool for identifying a new class of antiviral drugs.National Institute of Allergy and Infectious Diseases (NIAID)