Small molecule inhibitors as countermeasures for botulinum neurotoxin intoxication

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. Curre...

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Bibliographic Details
Published inMolecules Vol. 16; no. 1; pp. 202 - 220
Main Authors Li, Bing, Peet, Norton P, Butler, Michelle M, Burnett, James C, Moir, Donald T, Bowlin, Terry L
Format Journal Article Book Review
LanguageEnglish
Published Switzerland MDPI AG 30.12.2010
MDPI
Subjects
Acetylcholine - metabolism
Animals
Botulinum Toxins - antagonists & inhibitors
Botulinum Toxins - chemistry
Crystallography, X-Ray
drug discovery
Exocytosis
Humans
inhibitor
inum neurotoxin
Models, Molecular
Neuromuscular Junction - metabolism
Protein Conformation
Review
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Summary: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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules16010202