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Host defence peptides from neuroendocrine cells as a new source of anti-HIV compounds

Final Report Summary - PEPTHIV (Host defence peptides from neuroendocrine cells as a new source of anti-HIV compounds)

The AIDS pandemic has been a major challenge to global health for nearly three decades. According to current estimates, over 34 million people are still living with HIV worldwide. Although the introduction of antiretroviral therapy (HAART) has considerably reduced HIV-related mortality rates, HAART fails to achieve complete viral clearance. Besides advances in the treatment of HIV infection, numerous efforts have been made on HIV prevention. However, despite extensive research, no prophylactic HIV vaccine has emerged to date. Topical HIV microbicides have been developed as a highly promising strategy to moderate HIV transmission and allow women to take control of their own sexual heath. However, a safe and efficient anti-HIV microbicide is not yet available. As a consequence, innovative approaches to develop new HIV microbicides or improve HAART are critical.
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.