INEF

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

Coordinatore	UNIVERSITEIT GENT    more  Organization address address: SINT PIETERSNIEUWSTRAAT 25 city: GENT postcode: 9000 contact info Titolo: Prof. Nome: Bruno Cognome: Verhasselt Email: send email Telefono: -93322194 Fax: -93324953
Nazionalità Coordinatore	Belgium [BE]
Totale costo	3˙262˙293 €
EC contributo	2˙470˙540 €
Programma	FP7-HEALTH Specific Programme "Cooperation": Health
Code Call	FP7-HEALTH-2007-A
Funding Scheme	CP-FP
Anno di inizio	2008
Periodo (anno-mese-giorno)	2008-01-01   -   2011-06-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITEIT GENT  Organization address address: SINT PIETERSNIEUWSTRAAT 25 city: GENT postcode: 9000 contact info Titolo: Prof. Nome: Bruno Cognome: Verhasselt Email: send email Telefono: -93322194 Fax: -93324953	BE (GENT)	coordinator	0.00
2	ECOSYNTH  Organization address address: STATIONSTRAAT 123 city: OOSTENDE postcode: 8400 contact info Titolo: Dr. Nome: Koen Cognome: Van Aken Email: send email Telefono: +32 59 550235 Fax: +32 59 562172	BE (OOSTENDE)	participant	0.00
3	HELSINGIN YLIOPISTO  Organization address address: YLIOPISTONKATU 4 city: HELSINGIN YLIOPISTO postcode: 14 contact info Titolo: Prof. Nome: Kalle Cognome: Saksela Email: send email Telefono: +358- 9 191 26770 Fax: +358 9 191 26491	FI (HELSINGIN YLIOPISTO)	participant	0.00
4	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)  Organization address address: 101 Rue de Tolbiac city: PARIS postcode: 75654 contact info Nome: Mihaja Cognome: Auguste Email: send email Telefono: 01 48 07 34 18 Fax: 01 48 07 34 32	FR (PARIS)	participant	0.00
5	INSTITUT PASTEUR  Organization address address: RUE DU DOCTEUR ROUX 25-28 city: PARIS CEDEX 15 postcode: 75724 contact info Titolo: Dr. Nome: Nadia Cognome: Khelef Email: send email Telefono: +33 1 40 61 33 78 Fax: +33 1 40 61 39 40	FR (PARIS CEDEX 15)	participant	0.00
6	INSTITUTES DE RECHERCHES CLINIQUES DE MONTREAL  Organization address address: "110, avenue des Pins Ouest" city: MONTREAL postcode: H2W 1R7 contact info Titolo: Dr. Nome: Louis-Gilles Cognome: Durand Email: send email Telefono: -7066 Fax: -7205	CA (MONTREAL)	participant	0.00
7	MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.  Organization address address: Hofgartenstrasse 8 city: MUENCHEN postcode: 80539 contact info Nome: Barbara Cognome: Dobruchowski Email: send email Telefono: -2822 Fax: -2910	DE (MUENCHEN)	participant	0.00
8	UNIVERSITAET ULM  Organization address address: HELMHOLTZSTRASSE 16 city: ULM postcode: 89081 contact info Titolo: Mr. Nome: Frank Cognome: Gleixner Email: send email Telefono: -50067079 Fax: -50067074	DE (ULM)	participant	0.00
9	UNIVERSITE DE STRASBOURG  Organization address address: rue Blaise Pascal 4 city: Strasbourg postcode: 67070 contact info Nome: Laurence Cognome: Petin-Monteil Email: send email Telefono: +33 3 88 41 43 48 Fax: +33 3 68 85 42 20	FR (Strasbourg)	participant	0.00

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 Obiettivo del progetto (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'

Introduzione (Teaser)

Despite the development of anti-retroviral therapy, which controls the progression of HIV infections, the number of infected individuals on a global scale continues to rise. The continued evolution of viral immune pathology and the emergence of drug resistance urge the development of alternative treatment strategies.