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Content archived on 2024-05-27

Inhibiting Nef: a novel drug target for HIV-host interactions

Objective

Although HIV-1 Nef was originally named "negative factor," it has been shown to be critical for efficient persistance of HIV-1 infected humans thus playing a major role in the progression to AIDS. Remarkably; until now Nef has not been evaluated as an antiretroviral drug target. It is well established that Nef promotes HIV-1 replication and facilitates viral immune evasion by interacting with various host factors. Disrupting these essential interactions may delay or even prevent disease progression. Partners in this consortium have already identified small molecule inhibitors targeting Nef function. The first objective of this project is therefore to validate the molecular events elicited by these molecules in both virus-free as well as in HIV infection in vitro assays. In a complementing approach, small compound libraries already available to the consortium will be used and adapted to screen for inhibitors of Nef induced modulation of cellular receptors, NFAT activation and the Nef SH3 binding domain, that likely contribute to the importance of Nef in HIV-1 pathogenicity. In addition, functional screenings to discover drugable cellular Nef partners using RNA interference libraries will be performed. After validation of their importance in relation to the established host proteins co-interacting in the Nef cellular pathways, a selection will be additionally targeted by the developed small molecule inhibitors. Our ultimate goal is to deliver a complementary portfolio of candidate drugs that target the most important parameters in the Nef-host interaction pathway. Critical cellular interaction partners are much more conserved than viral enzymes that are usually targeted in highly-active-antiretroviral therapy (HAART). Therefore, it is believed by the partners that the novel approach presented in this project proposal will yield compounds less likely to be subject to the occurrence of drug resistance

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

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FP7-HEALTH-2007-A
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

CP-FP - Small or medium-scale focused research project

Coordinator

UNIVERSITEIT GENT
EU contribution
€ 605 520,00
Address
SINT PIETERSNIEUWSTRAAT 25
9000 Gent
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

No data

Participants (8)

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