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Targeting assembly of infectious HIV particles (HIV ACE)
Start date: 01 Mar 2008, End date: 31 Aug 2011 PROJECT  FINISHED 

"AIDS remains one of the major life threatening infectious diseases in the world today. A constant supply of novel antiretrovirals (ARVs) is needed to respond to the limitations of current drugs. By the end of 2007, the therapeutic arsenal against HIV is expected to comprise ARVs blocking all major steps of HIV replication, except for particle assembly and budding. Members of HIV-ACE were instrumental in recent breakthroughs concerning virus assembly and Envelope incorporation into virions. On the basis of novel and fully validated targets, the objectives of HIV-ACE are: i) Assay development, drug screening and pre-clinical development of small molecule inhibitors of Capsid assembly and Env incorporation, up to the stage of Early Drug Candidates with acceptable toxicity profile determined by ADME/Tox studies, activity against multi drug-resistant viral strains and primary non-B isolates, antiviral activity in primary T cells and macrophages (WP1); ii) Elucidation of 3D structures of these validated targets and rational drug design guided by molecular modelling and docking of inhibitors (WP2); iii) validation and exploitation of the HIV-susceptible transgenic rat model to allow preclinical in vivo-evaluation of novel drug candidates from HIV-ACE and to provide the European pharmaceutical industry with an efficient in vivo-platform for predictive testing of any kind of anti-HIV drug (WP3); iv) Elucidation of the mechanisms responsible for activity of the validated inhibitors, and discovery/validation of novel targets in the budding pathway of HIV-1 (WP4). HIV-ACE is composed of 8 teams from 5 European countries, including a Biopharma SME, led by prominent world-class scientists in Virology, Cell Biology, Immunology, Organic and Medicinal Chemistry, working in highly regarded research organisations. To efficiently achieve the ambitious goals of HIV-ACE, strong management led by a very experienced organisation has been included in a separate coordination-management WP5."
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