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 transcrip tase 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 va riants. Our 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-t hroughput 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 she d new light into the molecular mechanisms of virus budding, thereby rendering this critical step in HIV life cycle a feasible target for drug development. We are currently designing two assays allowing screening of libraries of chemicals. One is a cell-b ased assay and the other is a cell-free, protein/protein interaction assay. These assays do not require the use of infectious virus. Two libraries of 20,000 and 4,000 compounds, respectively, will be screened. We hope that these two complementary assays will allow the identification of hits or lead compounds, which could in a further step be improved by using a classical drug design approach.
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Funding SchemeSTREP - Specific Targeted Research Project