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Abstract

Grant Number:	5R43AI051134-02
PI Name:	GARDNER, JASON P.
PI Email:	jgardner@progenics.com
PI Title:
Project Title:	Development of Hepatitis C Virus entry inhibitors

Abstract: DESCRIPTION (provided by applicant): The development of new therapeutic agents for hepatitis C virus (HCV) infection is a major public health priority. We have selected HCV entry as a target for the discovery and development of novel antiviral agents. The overall goal of this Phase I project is to develop a novel cell-based membrane fusion assay that accurately recapitulates HCV entry, using well characterized, biologically relevant cellular reagents.During the Phase I project, we will develop stable cell lines that express fusogenic forms of native HCV envelope glycoproteins, and use these cells to adapt a cell-based membrane fusion assay for HCV entry. We will generate stable human hepatocyte cell lines as appropriate targets for fusion, and optimize the assay for reproducibility, sensitivity and suitability for high-throughput screening (HTS). We will also probe the mechanism of HCV entry using monoclonal antibodies and cell lines expressing putative attachment receptors.Success in the Phase I project will enable the HCV membrane fusion assay to be utilized in Phase II for HTS of libraries of structurally diverse small molecules, in order to identify potent inhibitors of HCV entry. Lead compounds will be screened for in vivo inhibition of HCV infection in a novel transgenic mouse model and mechanisms of action will be probed. Promising compunds will be developed for clinical application for HCV infection.

Thesaurus Terms:
antiviral agent, bioassay, hepatitis C virus, liver cell, technology /technique development, transfection, virus envelope, virus infection mechanism
drug screening /evaluation, glycoprotein, hepatitis C, high throughput technology, monoclonal antibody
cell line, clinical research, human tissue

Institution:	PROGENICS PHARMACEUTICALS, INC.
	777 OLD SAW MILL RIVER RD
	TARRYTOWN, NY 10591
Fiscal Year:	2003
Department:
Project Start:	15-SEP-2002
Project End:	31-AUG-2004
ICD:	NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG:	ZRG1

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