A small molecule screen to target viral RNA-protein complexes
Agency: Department of Health and Human Services
Agency Tracking Number: AI076143
Phase: Phase I
Awards Year: 2008
Solicitation Year: 2008
Solicitation Topic Code: N/A
Solicitation Number: PHS2007-2
Small Business Information
ADVANCED GENETIC SYSTEMS, INC.
ADVANCED GENETIC SYSTEMS, INC., 1554 25TH AVE, SAN FRANCISCO, CA, 94122
HUBZone Owned: Y
Woman Owned: Y
Socially and Economically Disadvantaged: Y
Phone: () -
Phone: (415) 806-0187
AbstractDESCRIPTION (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.
* information listed above is at the time of submission.