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TRIoH


HIV/AIDS

Targeting Replication and Integration of HIV
Framework programme:
6
Call:
1
Project number:
LSHB-CT-2003-50348
EC contribution:
€ 11,610,500
Duration:
42 months
Type:
IP
Starting date:
1 January 2004
Website:
http://www.kuleuven.ac.be/molvirgen/projects/
trioh/indextr.htm

Keywords: HIV; AIDS; antiviral therapy; entry; reverse transcriptase; nucleocapsid; integrase; cellular co-factors; mechanism of action; resistance; chemistry; modelling; genomics; animal models

Summary:

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 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.
TRIoH integrates different research efforts from different European partners on novel anti-HIV molecules targeting viral replication and integration. One main approach is multidisciplinary proteomics to study the basic science of HIV replication and integration, with special focus on the identification of new, cellular host factors. Our basic science, biotechnology and provocative chemistry will guide the development of new HIV therapeutics, leading to the development of new pre-clinical phase I compounds by our participating partners. Drug development will include all aspects of present day drug development: chemical synthesis, drug evaluation in enzymatic and cell culture assays, modelling and co-crystallisation, mechanism of action studies including biophysical measurements, antiviral resistance development and analysis, toxicological and pharmacological evaluation in cell culture and animal models.

Background:

The TRIoH consortium consists of HIV researchers that employ basic insight into the molecular virology of HIV and use advanced technologies of post-genomics, bio-informatics and biotechnology. These partners are experts in Europe to develop new technologies for accelerating anti-HIV drug development and novel anti-HIV drugs for the health of all people already infected with HIV or threatened to be infected in Europe and throughout the world, including people in developing countries.There is a close interaction between all involved scientific fields (chemistry, modelling, genomics, virology, structural biology, molecular biology, biochemistry, cell biology, biotechnology, pharmacology, toxicology) and our participating European research laboratories are integrated within these activities.

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