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Abstract

Grant Number: 1R43AI052668-01
PI Name: SALZWEDEL, KARL D.
PI Email: ksalzwedel@panacos.com
PI Title:
Project Title: Identification of Small Molecule Inhibitors of RSV Entry

Abstract: DESCRIPTION (provided by applicant): Respiratory syncytial virus (RSV) is a major cause of pediatric respiratory disease, resulting in severe lower respiratory tract infection in infants, immunocompromised patients and the elderly. There are no effective antiviral therapies for this disease although an immunoprophylactic antibody is available which reduces the severity of infection in high-risk infants. The development of new therapies for the treatment of RSV infection is a high priority. The initial steps in RSV infection include binding to the target cell and fusion with the cell's plasma membrane. Like HIV, RSV utilizes a protein structure termed a six-helix bundle to drive this membrane fusion event. Disruption of the six-helix bundle formation blocks fusion and infection. The goal of this Phase I project is to develop a prototype screening assay suitable for identifying small molecule inhibitors of RSV six-helix bundle formation. To accomplish this we will develop reagents for the selective detection of the RSV six-helix bundle and characterize the formation of this structure during the initial stages of fusion. This information will be used to develop a prototypic screening assay that will be suitable for use in a high-throughput screening format to detect RSV fusion inhibitors.

Thesaurus Terms:
antiviral agent, drug discovery /isolation, high throughput technology, membrane fusion, respiratory syncytial virus, technology /technique development, virus infection mechanism
conformation, synthetic protein
enzyme linked immunosorbent assay, immunoprecipitation, western blotting

Institution: PANACOS PHARMACEUTICALS, INC.
209 PERRY PKY
GAITHERSBURG, MD 20877
Fiscal Year: 2002
Department:
Project Start: 01-JUL-2002
Project End: 31-DEC-2002
ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG: ZRG1


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