Identification of mechanism of action of anti‐HIV properties of compounds present in Neem (Azadirachta indica) extracts

Abstract

Neem (Azadirachta indica) is a tree in the mahogany family Meliaceae. It is one of two species in the genus Azadirachta, and is native to Indian subcontinent. In India, Neem is widely regarded as “village pharmacy” because almost each part of the plant has been used for several different medicinal purposes. Neem extract prepared from its bark, leaf and seed has been shown to possess anthelmintic, antifungal, antibacterial, and anti‐malarial properties. Recently, in an in vitro study crude extract prepared from Neem leaves showed anti‐HIV‐1 activity. However the exact mechanism of action of this remains unknown. Hence the major goal of this project is to identify the molecular target of anti‐HIV1 action of Neem compounds. We hypothesize that compounds found in Neem may interact with various proteins essential for either entry or replicative life cycle of the HIV‐1 virus. Using structural bioinformatics approaches a small database of all the compounds known to present in crude extracts of Azadirachta indica was created. In silico docking was next used to study binding affinity of these compounds with several different molecular target proteins important in HIV‐1 life cycle viz. gp41 entry protein, reverse transcriptase, integrase and protease. Predicted binding affinity and interaction pattern emerged from in silico studies was further used to match compounds with their most likely protein target. Interestingly, our deductive analyses showed that most compounds present in Neem extract interact very strongly with HIV‐1 protease, hence making it plausible molecular target. In vitro assays are currently underway to further verify our in silico data. This research is supported by funds from Kean University and Ronald E. McNair Scholars Program.