Planta Med 2015; 81 - PK12
DOI: 10.1055/s-0035-1556290

Identification of novel inhibitors of botulinum neurotoxin A

C Yalamanchili 1, 2, VK Manda 1, AG Chittiboyina 1, WA Harrell Jr 3, RP Webb 3, IA Khan 1, 2, 3
  • 1National Center for Natural Products Research
  • 2Divison of Pharmacognosy, Department of BioMolecular Sciences, The University of Mississippi, University, MS, 38677, USA
  • 3US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702 – 5011, USA

The current post-exposure treatment of botulism using antitoxins is ineffective to treat the already neuron-internalized botulinum neurotoxin. Our aim is to find novel small-molecule 'phytochemical' inhibitors of Botulinum neurotoxin serotype A (BoNT A). Fifteen plants were selected from 'traditional medicine' based on symptoms similar to botulism. Around 850 phytochemicals from these fifteen plants were virtually screened in silico in five BoNT A-inhibitor crystal structures. From the in silico output, top 50 compounds were selected based on their docking scores, visual inspection and structural diversity. These compounds were screened in vitro by HPLC-BoNT A LC protease bioassay. Based on the in vitro results, seven compounds were further screened using the mouse phrenic nerve-hemidiaphragm ex vivo assay. At 20µM, NPC-ACA-3 showed marginal protection against BoNT A. The details of the workflow along with the in vitro and ex vivo data will be presented.