The purpose of the outlined research proposal is to search for novel marine natural products that inhibit the human immunodeficiency viruses (HIV type 1 and HIV type 2), the viruses responsible for human acquired immunodeficiency syndrome (AIDS), thus contributing to the urgent need to find new potent anti AIDS drugs. These unique compounds will be isolated from the organisms inhabiting the coral reefs of the Red Sea, an extremely diverse habitat, which offers a unique advantage, in view of the high endemism of its flora and fauna. The compounds (some of which have already been shown to be effective) will be purified, chemically characterized and subsequently tested for blocking two key steps in the early life cycle of HIV, i.e., the reverse transcription and the integration process. The inhibition studies will be carried out first in vitro with purified HIV-1 and HIV-2 reverse transcriptases and integration proteins. The most potent and specific compounds will be further analyzed in tissue cultures to assess their anti-HIV activity and their cytotoxicity to normal cells. In parallel, we shall chemically modify the functional sites of the active compounds for structure-activity relationship studies in order to improve their specific anti-HIV activity (hence, increasing their potency and decreasing their toxicity. The most potent and specific substances will hopefully lead to the development of new anti-AIDS drugs.
