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Abstract
Grant Number: 1R03MH082403-01A1 Project Title: A Cell Based HTS Approach for the Discovery of New Inhibitors of RSV
PI Information: Name Title SEVERSON, WILLIAM E. severson@sri.org Abstract: DESCRIPTION (provided by applicant): Currently, there are no commercially available vaccines to protect humans against Respiratory syncytial virus (RSV) infection. RSV is associated with substantial morbidity and mortality and is the most common cause of bronchiolitis and pneumonia among infants and children under one year of age. Since humans have no immunity against RSV infection, severe lower respiratory tract disease may occur at any age, especially among the elderly or among those with compromised cardiac, pulmonary, or immune systems. The existing therapies for the acute infection are ribavirin, which has inconsistent clinical results, and the prophylactic humanized monoclonal antibody (Synagis(r) from MedImmune) that is expensive and limited to use in high risk pediatric patients. The economic impact of RSV infections due to hospitalizations and indirect medical costs is approximately > $ 650 million annually. Thus, there is a critical need to discover novel antiviral drugs to supplement existing chemotherapeutics. A high throughput screening (HTS) approach provides an opportunity to screen large compound libraries in vitro. We have developed and validated a 384-well cell-based assay that measures CPE induced in HEp-2 cells by RSV infection, using a luminescent-based detection system for signal endpoint. This molecular HT molecular screen will provide the foundation for secondary dose response assays that will divulge critical antiviral potency and cytotoxicity information on active compounds and bestow the scientific community with assays that allow for the rapid identification of potential inhibitors of RSV by evaluating large compound libraries in vitro.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
high throughput technology, respiratory syncytial virus
cytotoxicity, drug discovery /isolation, peptide library
NIH Roadmap Initiative tag
Institution: SOUTHERN RESEARCH INSTITUTE 2000 NINTH AVENUE SOUTH BIRMINGHAM, AL 35205 Fiscal Year: 2007 Department: Project Start: 29-SEP-2007 Project End: 31-AUG-2009 ICD: NATIONAL INSTITUTE OF MENTAL HEALTH IRG: ZMH1