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A small molecule screen to target viral RNA-protein complexes

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
88720
Program Year/Program:
2008 / SBIR
Agency Tracking Number:
AI076143
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
ADVANCED GENETIC SYSTEMS, INC.
1554 25TH AVE SAN FRANCISCO, CA 94122-3320
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2008
Title: A small molecule screen to target viral RNA-protein complexes
Agency: HHS
Contract: 1R43AI076143-01A1
Award Amount: $238,974.00
 

Abstract:

DESCRIPTION (provided by applicant): There is a significant need for novel HIV therapies given the emergence of viruses resistant to existing drug regimens. RNA-protein complexes represent an important and under utilized drug target. In HIV, the Tat-TAR an d Rev-RRE RNA- protein complexes carry out essential roles in RNA transcription and nuclear export respectively. Disruption of these RNA-protein complexes can inhibit viral replication, thus this strategy holds great promise for antiviral drug discovery. A dvanced Genetic Systems (AGS) and UCSF have jointly developed a cell- based drug-screening platform to target RNA and RNA-protein complexes. The screening platform was rigorously evaluated with control inhibitors and a pilot screen of 4500 small molecule c ompounds targeting Rev-RRE. From this screen, we identified novel compounds that specifically target Rev, exhibit low toxicity, display favorable pharmacokinetic properties, and inhibit HIV replication at sub-micromolar IC50s. This result has given us grea t confidence that we have developed a high-quality, robust screening platform capable of identifying inhibitors of viral RNA-protein targets. We now wish to use our screening platform to carry out expanded screens targeting HIV Rev- RRE and Tat-TAR. We wil l screen a small molecule diversity library to identify new molecular entities that could form the basis of new classes of anti-HIV therapeutics. PUBLIC HEALTH RELEVANCE: There is significant need to develop new classes of antiviral drugs to combat emerging viral diseases and resistance to older drugs. RNA-protein complexes represent an important and under utilized viral drug target. Disruption of an RNA-protein complex can inhibit viral replication, thus this strategy holds great promise for antivi ral drug discovery.

Principal Investigator:

Business Contact:

Small Business Information at Submission:

ADVANCED GENETIC SYSTEMS, INC.
ADVANCED GENETIC SYSTEMS, INC. 1554 25TH AVE SAN FRANCISCO, CA 94122

EIN/Tax ID: 320080584
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No