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Project Summary
Context - Insight - Objectives - Method
Standard therapy of infection with the human immunodeficiency virus type 1 (HIV-1) is based on potent cocktails of drugs targeting viral proteins. This treatment is associated with severe side effects and is almost unaffordable for the patients living in sub-Saharan Africa. Moreover, incomplete suppression of HIV replication results in emergence of drug-resistant strains. Therefore, a continued research effort is required to develop more potent, cheaper and less toxic antivirals.
The insight has grown that HIV requires multiple cellular proteins to serve as co-factors for viral replication. Our over-all objective is to develop novel treatment strategies by targeting cellular proteins required for HIV replication. The virus may find more difficulties in developing antiviral resistance against drugs targeting interaction between invariable cellular proteins and conserved viral protein domains. We will focus on the cellular proteins that mediate HIV trafficking, nuclear import and integration. Recently, we identified and validated Lens Epithelium Derived Growth Factor (LEDGF/p75) as a novel cofactor of HIV-1 integration and replication. Our multidisciplinary consortium is composed of 3 biologists/virologists, 3 medicinal chemists, 1 virologist from South Africa, 1 structural biologist and 1 pharmaceutical company (left in 2010). The project will also increase our basic understanding of protein-protein interactions (PPI) during HIV infection.
Our first objective is to identify and validate novel co-factors of HIV trafficking, nuclear import and integration as novel targets for future anti-HIV therapy.
The second objective is to develop new drugs against the recently validated cellular target LEDGF/p75.
The third objective is to perform this work in the perspective of those who will benefit most: the HIV infected people all over the world.
The initial steps of target validation and hit identification should be taken by academia supported by public funding. However, further optimization and (pre)clinical development of drugs are ideally undertaken in close collaboration with industry, hence the participation of Tibotec, an international company with main research and development laboratories located in Belgium, devoted to development of antiviral drugs.
Administrational information
Project number: HEALTH-2007-2.3.2-1
GA number: HEALTH-F3-2008-201032
EC contribution: 2,939,672.00 €
Duration: 48 months
Starting date: 01/03/2008
