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NEWHIVTARGETS


HIV/AIDS

Identifying novel classes of HIV inhibitors
Framework programme:
6
Call:
2
Project number:
LSHP-CT-2004-012169
EC contribution:
€ 550,000
Duration:
24 months
Type:
STREP
Starting date:
1 January 2005

Keywords: Screening assays; HTS; HIV; antiviral drugs; viral release

Summary:

Despite the success of highly active antiretrovirals to control HIV replication in infected patients, at least in countries that can afford these treatments, new drugs are still needed. Widely used drugs mainly target two viral enzymes, reverse transcriptase and protease. However, about 20% of patients cannot tolerate antiviral cocktails in the short term, and long-term treatments are often associated with severe side effects. There is also increasing concern about the spreading of drug-resistant HIV variants.

The aim is to identify lead compounds that could impact HIV through new mechanisms. Academia experts in virology and cellular biology have joined forces with antiviral-research specialists and pharmacologists, in order to perform anti-HIV high-throughput screening (HTS) assays. We have defined one unexploited viral target, for which there are no available inhibitors: the critical step of viral release from the cell. This novel target has been chosen because important recent discoveries have shed new light into the molecular mechanisms of virus budding, thereby rendering this critical step in the HIV life cycle a feasible target for drug development.

Two assays are currently being designed to allow the screening of libraries of chemicals. One is a cell-based assay and the other is a cell-free, protein/protein interaction assay. These assays do not require the use of an infectious virus. Two libraries of 20 000 and 4 000 compounds respectively will be screened.

It is hoped that these two complementary assays will allow the identification of hits or lead compounds, which could be improved by using a classical drug design approach.

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