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THINC


HIV/AIDS

Targeting hiv integration co-factors, targeting cellular proteins during nuclear import or integration of hiv
 
 
Framework programme:
 7
Contract/Grant agreement number:
222948
EC contribution:
2,900,000 €
Duration:
48 months
Funding scheme:
Focused research project
Starting date:
01/03/2008
Project web site:
http://www.kuleuven.be/molmed/thinc/index.htm
 
 

Keywords: HIV, AIDS, Drug discovery, cellular co-factors, LEDGF, integration

Background

The standard therapy for infection with the human immunodeficiency virus type 1 (HIV-1) is based on a potent cocktail of drugs targeting viral proteins. This treatment is associated with severe side effects and is almost unaffordable for sub-Saharan Africans. Incomplete suppression of HIV replication results in drug resistance; therefore, a continued research effort is required to develop more potent, cheaper and less toxic antivirals.

It is now believed that HIV requires cellular proteins to serve as co-factors for viral replication. The overall objective of THINC is to develop novel drugs by targeting co-factors required for HIV replication. The virus will find it difficult to develop antiviral resistance against drugs targeting interaction between invariable cellular proteins and conserved viral protein domains. THINC will focus on the cellular proteins that mediate HIV trafficking, nuclear import and integration, such as Lens Epithelium Derived Growth Factor (LEDGF/p75), a novel cofactor of HIV-1 integration.

Aims and expected results

The first objective is to identify and validate novel co-factors of HIV trafficking, nuclear import and integration as novel targets for anti-HIV therapy. The second objective is to develop new drugs against the validated cellular target LEDGF/p75. The third objective is to perform this work in the perspective of those who will benefit most: HIV-infected people worldwide. The initial steps of target validation, hit identification and optimisation will mainly be taken by academic groups, while (pre)clinical development of drugs requires partnerships with European companies devoted to the development of antiviral drugs. The project will also increase generic understanding of protein-protein interactions (PPIs). The fourth objective is to develop novel treatment strategies by targeting cellular proteins required for HIV replication.

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