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Trana Discovery and Southern Research Institute Find Bioactive HIV Antiviral Compounds
Date:10/28/2009

NIAID contracts additional $700,000 to screen 300,000 more compounds for HIV inhibition

CARY, N.C. and BIRMINGHAM, Ala., Oct. 28 /PRNewswire-USNewswire/ -- Trana Discovery, Inc., an infectious disease drug discovery technology company, and Southern Research Institute, a not-for-profit contract research organization conducting basic and applied preclinical drug research, today announced that several bioactive hits from a set of 15,000 diverse small molecule compounds screened under contract with the National Institute of Allergy and Infectious Diseases (NIAID) exhibit antiviral activity against HIV-1 infected cells. Among the compounds tested at Southern Research using the Trana HIV 201 High-Throughput Screening (HTS) assay, 16 compounds demonstrated inhibition of HIV replication in infected human cells and several of these compounds were judged to be "potentially druggable."

The screening assay used to identify the compounds is based on the premise that HIV-1 has evolved to use tRNALys3 as a primer for initiation of reverse transcription. Therefore, the interaction between tRNALys3 and viral genomic RNA represents a potential novel target for HIV-1 drug development. The biochemical assay to identify inhibitors of the interaction between tRNALys3 and HIV-1 genomic RNA was developed by Trana and transferred to Southern Research for high-throughput screening. Southern Research converted the assay to a homogeneous amplified luminescent proximity assay using AlphaScreen(R) reagents from PerkinElmer.

During this initial pilot study, 164 compounds were identified from the diversity set library as hits. Of these hits, 136 were retested in dose-response against HIV-1IIIB replication in a CEM-SS cytoprotection assay. Sixteen of this last group of compounds inhibited HIV-1 rep
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SOURCE Southern Research Institute
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