Final Report Summary - PEPTHIV (Host defence peptides from neuroendocrine cells as a new source of anti-HIV compounds)
Host defense peptides (HDPs) constitute an exciting class of drug candidates, especially because they are unlikely to induce drug resistance. HDPs constitute important components of the innate host defense against a broad spectrum of pathogens. To date, several natural HIV inhibitors have been characterized. However, systematic screens for naturally occurring anti-HIV compounds have been a major failure due to technical issues but also to a limited accessibility of fluids, tissues or organelles enriched in HDPs. Secretory granules of neuroendocrine cells are particularly enriched in HDPs and therefore constitute an excellent model to screen new anti-HIV compounds. The PEPTHIV project was design to identify new anti-HIV candidates derived from neuroendocrine peptides for the development of a microbicide gel against HIV or to improve HAART. Indeed, we identified a safe and efficient peptidic lead compound that repressed HIV replication through inhibition of the HIV protease. In addition, two molecules derived from this lead compound were synthesized and show a better efficacy than the lead compound and no toxicity.