A NOVEL ASSAY FOR THE DETECTION OF ANTIVIRAL DRUGS

VIRAL PROLIFERATION REQUIRES THE INTERACTION OF VIRAL REGULATORY PROTEINS WITH THEIR COGNATE RECOGNITION SEQUENCESWITHIN THE VIRAL GENOME. THIS RESEARCH SEEKS TO IDENTIFY SMALL MOLECULES THAT WILL INTERFERE WITH THESE DNA PROTEIN INTERACTIONS BY BINDING IN A SEQUENCE-SPECIFIC MANNER TO THE DNA RECOGNITION SITE. TOWARD THIS GOAL, GENELABS, INC., WILL DEVELOP A BINDING INHIBITION ASSAY THAT WILL BE USED TO SCREEN LARGE LIBRARIESOF BIOLOGICAL AND SYNTHETIC CHEMICALS FOR THE ABILITY TO DISRUPT SPECIFIC DNA:PROTEIN COMPLEXES. IN PHASE I, THE FEASIBILITY OF ASSAY DEVELOPMENT WILL BE TESTED; IN PHASE II, THE PRIMARY SCREENING ASSAY WILL BE DEVELOPED. LATER, CORPORATE INTERACTIONS WITH COMPANIES POSSESSING LIBRARIES WILL BE ESTABLISHED AND LIBRARIES WILL BE SCREENED. THE SPECIFIC GOALS OF PHASE I ARE TO (1) DESIGN A MODEL ASSAY SYSTEM FOR DEVELOPMENT IN PHASE II, AND (2) DEMONSTRATE FEASIBILITY BY SHOWING THAT THE BINDING OF A COMPETING MOLECULE BLOCKS THE BINDING OF A REGULATORY PROTEIN. ALTHOUGH THE TEST SYSTEM CHOSEN FOR THESE PRELIMINARY STUDIES IS THE BINDING OF EBNA TO THE ORI-P SITEOF EPSTEIN-BARR VIRUS, THE SCREENING ASSAY WILL BE APPLICABLE TO A WIDE ARRAY OF MEDICALLY SIGNIFICANT VIRUSES.