ANTIVIRAL SCREENING ASSAYS BASED ON HCV REPLICONS

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 2R44AI049604-02
Agency Tracking Number: AI049604
Amount: $750,000.00
Phase: Phase II
Program: SBIR
Awards Year: 2002
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
APATH, LLC
893 N. WARSON RD., ST. LOUIS, MO, 63141
DUNS: N/A
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 PAUL OLIVO
 (314) 812-8144
 OLIVO@APATH.COM
Business Contact
 L MILTON
Phone: (314) 812-8160
Email: MILTON@APATH.COM
Research Institution
N/A
Abstract
DESCRIPTION (Provided by applicant): Hepatitis C virus (HCV) is the most prevalent chronic blood-borne infection in the U.S and a global health problem. Approximately 4 million individuals in the U.S. and 170 million individuals worldwide are chronically infected. As much as 40 percent of chronic liver disease is HCV related and this results in up to 10,000 deaths each year. Despite improvements, treatment of remains suboptimal, and new therapeutic options are critically needed. Apath, LLC has developed cell-based assays for testing and screening of compounds with antiviral activity against hepatitis C virus (HCV). These assays are based on Huh7 cell lines that contain a constructively replicating subgenomic HCV replicon. The cells have been analyzed extensively and have been demonstrated to contain an HCV replicon that exhibits autonomous HCV RNA replication. We have promoted these cell lines as drug-discovery tools by formatting assays for compound screening that are amenable to high throughput screening. In this Phase II proposal we describe our plans to use these cell-based assays to identify compounds with anti-HCV activity. Toward this goal we will plan to utilize a unique source of natural compounds and to screen over 40,000 wells containing up to 200,000 discrete compounds to identify "hits" that inhibit replication of the HCV replicon. We will confirm antiviral activity of all "hits" in secondary HCV replicon quantitation and cytotoxicity assays. We will identify compounds with the most promising chemical and biological profiles to pursue as potential anti-HCV drugs. We also plan to identify targets of leads through biochemical and genetic approaches.

* information listed above is at the time of submission.

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