Obiettivo 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 Campo scientifico medical and health scienceshealth sciencesinfectious diseasesRNA virusesHIVmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancenatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Parole chiave HIV Nef small molecule inhibitor Programma(i) FP7-HEALTH - Specific Programme "Cooperation": Health Argomento(i) HEALTH-2007-2.3.2-1 - HIV/AIDS Drug Discovery and Preclinical Development Invito a presentare proposte FP7-HEALTH-2007-A Vedi altri progetti per questo bando Meccanismo di finanziamento CP-FP - Small or medium-scale focused research project Coordinatore UNIVERSITEIT GENT Contributo UE € 605 520,00 Indirizzo SINT PIETERSNIEUWSTRAAT 25 9000 Gent Belgio Mostra sulla mappa Regione Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Bruno Verhasselt (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Partecipanti (8) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto UNIVERSITAET ULM Germania Contributo UE € 471 600,00 Indirizzo HELMHOLTZSTRASSE 16 89081 Ulm Mostra sulla mappa Regione Baden-Württemberg Tübingen Ulm, Stadtkreis Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Frank Gleixner (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato HELSINGIN YLIOPISTO Finlandia Contributo UE € 449 920,01 Indirizzo YLIOPISTONKATU 3 00014 Helsingin Yliopisto Mostra sulla mappa Regione Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Kalle Saksela (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato INSTITUT PASTEUR Francia Contributo UE € 448 920,00 Indirizzo RUE DU DOCTEUR ROUX 25-28 75724 Paris Mostra sulla mappa Regione Ile-de-France Ile-de-France Paris Tipo di attività Research Organisations Contatto amministrativo Nadia Khelef (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato ECOSYNTH Belgio Contributo UE € 248 039,99 Indirizzo INDUSTRIELAAN 12 9800 Deinze Mostra sulla mappa Regione Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Tipo di attività Private for-profit entities (excluding Higher or Secondary Education Establishments) Contatto amministrativo Koen Van Aken (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato INSTITUTES DE RECHERCHES CLINIQUES DE MONTREAL Canada Contributo UE Nessun dato Indirizzo 110, avenue des Pins Ouest H2W 1R7 MONTREAL Mostra sulla mappa Tipo di attività Research Organisations Contatto amministrativo Louis-Gilles Durand (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Germania Contributo UE € 164 360,00 Indirizzo HOFGARTENSTRASSE 8 80539 Munchen Mostra sulla mappa Regione Bayern Oberbayern München, Kreisfreie Stadt Tipo di attività Research Organisations Contatto amministrativo Barbara Dobruchowski Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato UNIVERSITE DE STRASBOURG Francia Contributo UE € 82 180,00 Indirizzo RUE BLAISE PASCAL 4 67081 Strasbourg Mostra sulla mappa Regione Grand Est Alsace Bas-Rhin Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Laurence Petin-Monteil Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Francia Contributo UE Nessun dato Indirizzo RUE DE TOLBIAC 101 75654 Paris Mostra sulla mappa Regione Ile-de-France Ile-de-France Paris Tipo di attività Research Organisations Contatto amministrativo Mihaja Auguste Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato