Volume 8 Issue 1
Small Molecule Inhibitors as Countermeasures for Botulinum Neurotoxin Intoxication
Bing Li,Norton P. Peet,Michelle M. Butler,James C. Burnett,Donald T. Moir andTerry L. Bowlin
1Microbiotix, Inc., One Innovation Drive, Worcester, MA 01605, USA
2Target, Structure-Based Drug Discovery Group, SAIC-Frederick, Inc., National Cancer Institute at Frederick, 1050 Boyles Street, Frederick, MD 21702, USA
*Author to whom correspondence should be addressed.
Abstract
Botulinum neurotoxins (BoNTs) are the most potent of known toxins and are listed as category A biothreat agents by the U.S. CDC. The BoNT-mediated proteolysis of SNARE proteins inhibits the exocytosis of acetylcholine into neuromuscular junctions, leading to life-threatening flaccid paralysis. Currently, the only therapy for BoNT intoxication (which results in the disease state botulism) includes experimental preventative antibodies and long-term supportive care. Therefore, there is an urgent need to identify and develop inhibitors that will serve as both prophylactic agents and post-exposure ‘rescue’ therapeutics. This review focuses on recent progress to discover and develop small molecule inhibitors as therapeutic countermeasures for BoNT intoxication.
Keywords: botulinum neurotoxin; inhibitor; drug discovery