The botulinum neurotoxin (BoNT), is a highly lethal toxin that causes neuromuscular paralysis and in severe cases death.  There are seven different serotypes of the neurotoxin (A-G), the serotypes most associated with human botulism are A, B and E.  Our research group is working toward identifying small molecule inhibitors for the BoNT/E light chain.  Employing a high throughput assay we screened a small molecule library composed of FDA approved drugs or compounds that have been involved in clinical trials.  The high throughput assay resulted in the identification of several FDA approved drugs that inhibited the BoNT/E light chain.  Currently we are evaluating the initial inhibitors in a HPLC assay.  The HPLC assay will validate the initial �hits� and determine their mode of inhibition.  Validated inhibitors will be optimized via substrate activity relationship studies (SAR) and computational analysis.

Discovery and optimization of small molecule inhibitors for the botulinum neurotoxin type E protease

243rd National Meeting (2012)

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