Small molecule inhibitors as countermeasures for botulinum neurotoxin intoxication |
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Authors: | Li Bing Peet Norton P Butler Michelle M Burnett James C Moir Donald T Bowlin Terry L |
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Institution: | Microbiotix, Inc., One Innovation Drive, Worcester, MA 01605, USA. bli@microbiotix.com |
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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. |
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