Anti-HIV drugs, used at present in the clinic, target the viral reverse transcriptase (RT) or protease (PR). Combination therapies are the current standard of care. However, as a result of insufficient drug plasma levels or of insufficient inhibitory power of the chosen drug combination, drug resistant strains emerge, resulting in therapeutic failure. Consequently, there is a continuing need for new anti-HIV drugs to be used in combination with the current drugs, which should represent novel chemical entities targeting known targets (viral entry,reverse transcription), or should act on new viral targets of the HIV replication cycle (e.g. nucleocapsid, integrase) or interfere with cellular co-factors required for HIV replication.
The general objective of TRIoH is to integrate the different research efforts from different European partners on novel anti-HIV molecules targeting viral replication and integration. Our central scientific paradigm is the molecular continuum between the different HIV early replication steps starting with viral entry and leading to integration. We will use multidisciplinary proteomics approaches to study the basic science of HIV replication andintegration. There is special focus on the identification of new, cellular host factors. Our research will foster a technological platform of academic and industrial partners and result in more efficient development of new drugs and therapies by providing new assays and new targets. Basic science, biotechnology and provocative chemistry will guide the development of new HIV therapeutics. Identified lead compounds of participating partners will be developed preclinically, ready for Phase 1 clinical trials. Different Biotech SMEs are actively involved in the development and valorisation program. Our project will include all aspects of present day drug development starting with chemical synthesis up to preclinical evaluation in animal models.
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