May 7th, 2008, Paris (France) – The HIV-ACE (ACE for Anti-Capsid assembly and Envelope incorporation) research project coordinated by Clarisse Berlioz-Torrent, team leader of an Inserm research team (Inserm Unit 567, Hospital Cochin, Infectious Diseases Unit, Paris) has been officially launched on Thursday 17th April in Paris. HIV-ACE is a European collaborative research project funded by the European Commission under the Health Work Programme of the 7th Framework Programme. This consortium brings together prominent world-class scientists in Virology, Cell Biology Immunology Organic and Medicinal Chemistry working in highly regarded European research organizations. The final goal of this consortium is to deliver at the end of the three year EC funding, innovative antiviral molecules at the stage of early drug candidates, well characterized concerning their antiviral activity and toxicity profile. Members of the HIV-ACE consortium have identified molecular targets crucial for the assembly of the viral Capsid and for the incorporation of the Envelope (cf. box, step 4). Those mechanisms are not addressed yet by any therapies and more importantly rely on interactions between proteins (host cell‘s and virus’) whereas most of the current drugs’ mechanism is to disrupt the viral enzymes. Today the combinations of drugs used in the Highly Active Antiretroviral Treatment (HAART) target mainly the viral enzymes (cf. box, steps 2, 3 and 5). However those therapeutic strategies are challenged by the high mutation rate of the viral enzymes, which is the main cause of viral resistance to treatments. By focusing on protein-protein interactions, the HIV-ACE project proposes a precursory therapeutic strategy. ------------------------------------------- * The viral cycle can be divided in 5 steps: 1-Viral entry through receptor/co-receptor recognition followed by fusion of the viral membrane with that of target cells; 2-Reverse transcription of the viral RNA into pro-viral DNA, catalyzed by the viral Reverse Transcriptase (RT); 3-Integration of the pro-viral DNA into the host cell genome (controlled by the viral Integrase (IN)) 4-Assembly and budding of new virus particles 5-Maturation of virions under the control of the viral protease (PR). -------------------------------------------- With over 35 millions infected people worldwide living with HIV and the continuous raise of resistance among viruses, there is a permanent need for new drugs and new class of drugs, such as the entry inhibitor and the intégrase inhibitor (step 1 and 3 of the viral cycle) available since the end of 2007. The HIV-ACE project aims at complementing this therapeutic arsenal against HIV with new molecules that are less likely to give raise to resistance. The HIV-ACE Consortium is coordinated by Inserm (French Health Institute), and comprises the Universitätsklinikum of Heidelberg (Germany), the Medical Research Council (UK), the Pasteur Institute (France), CellVir (a drug development SME established in France), the Institute of Organic Chemistry and Biochemistry (Czech Republic), the University of Geneva (Switzerland) and Inserm-Transfert (France).
Switzerland, Germany, France