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Antivirals Targeting Flavivirus Envelope Proteins

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI069664-01
Agency Tracking Number: AI069664
Amount: $998,224.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Solicitation Year: N/A
Award Year: 2006
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
United States
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (203) 737-2596
Business Contact
Phone: (203) 393-9439
Research Institution

DESCRIPTION (provided by applicant): The overall goal of this project is to develop therapeutic antivirals to treat life-threatening flavivirus infections. Enfuvirtide, a clinically successful peptide HIV fusion inhibitor, is the prototype for a new class of antivirals that inhibit viral envelope protein structural rearrangements essential for viral entry into host cells. In preliminary experiments, we screened a phage display library for proteins and peptides that bind recombinant West Nile (WN) virus envelope protein. WN virus peptides with affinity for envelope protein were also rationally selected from the envelope protein structure. These studies identified six proprietary peptides that bind recombinant WN virus envelope protein and inhibit WN virus infection of cultured cells. In this project, we will identify additional peptides that block WN and dengue virus infections. Selected peptides will be modified to produce broad-spectrum peptides that target multiple flaviviruses. The project will also initiate high throughput screening of chemical compound libraries for antiviral small molecules that compete with the neutralizing peptides for binding to envelope protein. Candidate antiviral compounds will be evaluated for neutralization of flaviviruses, including the four serotypes of dengue virus, and for ability to protect mice against dengue and WN virus infections. This experimental approach will be expanded in Phase II to develop a panel of modified peptides and small molecules that are candidates for development as human therapeutics. This project will provide clinicians and public health officials with new means to manage natural, accidental and intentional flavivirus outbreaks.

* Information listed above is at the time of submission. *

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