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Small molecule inhibitors as countermeasures for botulinum neurotoxin intoxication.

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.

SUBMITTER: Li B

PROVIDER: S-EPMC6259422 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Small molecule inhibitors as countermeasures for botulinum neurotoxin intoxication.

Li Bing B Peet Norton P NP Butler Michelle M MM Burnett James C JC Moir Donald T DT Bowlin Terry L TL

Molecules (Basel, Switzerland) 20101230 1

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 ne ...[more]

PMID: 21193845

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