Small Molecule Inhibitors as Countermeasures for Botulinum Neurotoxin Intoxication

• Main Authors: Terry L. Bowlin, Donald T. Moir, Michelle M. Butler, James C. Burnett, Bing Li, Norton P. Peet
• Format: Article
• Language: English
• Published: MDPI AG 2010-12-01
• Series: Molecules
• Subjects: inum neurotoxin; inhibitor; drug discovery
• Online Access: http://www.mdpi.com/1420-3049/16/1/202/

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.