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 medical and health scienceshealth sciencesinfectious diseasesRNA virusesHIVmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancenatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Keywords HIV Nef small molecule inhibitor Programme(s) FP7-HEALTH - Specific Programme "Cooperation": Health Topic(s) HEALTH-2007-2.3.2-1 - HIV/AIDS Drug Discovery and Preclinical Development Call for proposal FP7-HEALTH-2007-A See other projects for this call Funding Scheme CP-FP - Small or medium-scale focused research project Coordinator UNIVERSITEIT GENT EU contribution € 605 520,00 Address SINT PIETERSNIEUWSTRAAT 25 9000 Gent Belgium See on map Region Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Activity type Higher or Secondary Education Establishments Administrative Contact Bruno Verhasselt (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Participants (8) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITAET ULM Germany EU contribution € 471 600,00 Address HELMHOLTZSTRASSE 16 89081 Ulm See on map Region Baden-Württemberg Tübingen Ulm, Stadtkreis Activity type Higher or Secondary Education Establishments Administrative Contact Frank Gleixner (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data HELSINGIN YLIOPISTO Finland EU contribution € 449 920,01 Address YLIOPISTONKATU 3 00014 Helsingin Yliopisto See on map Region Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa Activity type Higher or Secondary Education Establishments Administrative Contact Kalle Saksela (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data INSTITUT PASTEUR France EU contribution € 448 920,00 Address RUE DU DOCTEUR ROUX 25-28 75724 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Administrative Contact Nadia Khelef (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data ECOSYNTH Belgium EU contribution € 248 039,99 Address INDUSTRIELAAN 12 9800 Deinze See on map Region Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Administrative Contact Koen Van Aken (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data INSTITUTES DE RECHERCHES CLINIQUES DE MONTREAL Canada EU contribution No data Address 110, avenue des Pins Ouest H2W 1R7 MONTREAL See on map Activity type Research Organisations Administrative Contact Louis-Gilles Durand (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Germany EU contribution € 164 360,00 Address HOFGARTENSTRASSE 8 80539 Munchen See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Administrative Contact Barbara Dobruchowski Links Contact the organisation Opens in new window Website Opens in new window Total cost No data UNIVERSITE DE STRASBOURG France EU contribution € 82 180,00 Address RUE BLAISE PASCAL 4 67081 Strasbourg See on map Region Grand Est Alsace Bas-Rhin Activity type Higher or Secondary Education Establishments Administrative Contact Laurence Petin-Monteil Links Contact the organisation Opens in new window Website Opens in new window Total cost No data INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE France EU contribution No data Address RUE DE TOLBIAC 101 75654 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Administrative Contact Mihaja Auguste Links Contact the organisation Opens in new window Website Opens in new window Total cost No data