Identification of novel phytochemical inhibitors of botulinum neurotoxin A

Botulinum neurotoxins (BoNTs), the causative agents of botulism are the most potent known toxins, and are classified as class A bioterror agents. BoNTs enter the blood stream and reach the neuromuscular junctions and inhibit the release of acetyl choline from the neurons, causing flaccid paralysis, which when left untreated can result in death from respiratory arrest. Post exposure treatment is limited to supportive care with antitoxin to remove the circulating toxin. However, antibody treatment is ineffective to treat the toxin internalized in to the neurons. Small molecule inhibitors provide an opportunity to treat botulism both before and after the cellular intoxication occurs. Our aim was to find novel small molecule phytochemical inhibitors of BoNT serotype A (BONT A), the most potent among the seven BoNT serotypes (A-G). We screened several phytochemicals selected based on traditional medicine using computer aided drug design. Compounds with the best docking scores were assayed with HPLC based in vitro screening. The research details of the virtual screening and the in vitro screening data will be presented.