title: Current strategies for designing antidotes against botulinum neurotoxins.
abstract: BACKGROUND
  Botulinum neurotoxins (BoNTs) are proteins responsible for the deadly paralytic disease botulism. Extreme toxicity, ease of production and lack of antidotes against BoNT makes it a category A biothreat agent, according to the United States Center of Disease Control and Prevention. The only available therapy for BoNT is an equine antitoxin antibody or/and a protracted respiratory support system. Even then, antibody treatment can only prevent further exposure of the toxin and cannot rescue already intoxicated neurons.
  
  
  METHODS
  In this article, the authors provide a summary of the current status of inhibitors and antitoxins used against BoNTs. In particular, the authors focus on new strategies used in the development of novel therapeutics. They also outline the major steps involved in BoNT's mechanism of action and identify specific inhibitors for each step.
  
  
  CONCLUSIONS
  Several previous efforts have resulted in less than satisfactory results that are due, in part, to a lack of sustained effort in addition to a poor understanding of the unique structural features of the toxin. BoNT is a double-edged sword with both toxic effects and therapeutic benefits, excluding vaccination as a preventative measure. The long lasting intracellular endopeptidase activity, which causes an extended period of muscle paralysis, necessitates the need to identify effective inhibitor(s) against BoNT, and this could ultimately lead to new therapeutic options.
authors: University of Massachusetts Dartmouth, Department of Chemistry and Biochemistry , North Dartmouth, MA 02747 , USA.
authors: Kruti
authors: K
authors: Patel
authors: Shuowei
authors: S
authors: Cai
authors: Bal Ram
authors: BR
authors: Singh
mesh_terms: D000818:Animals; D000931:Antidotes / Q000494:pharmacology / Q000627:therapeutic use; D001904:Botulinum Antitoxin / Q000494:pharmacology / Q000627:therapeutic use; D001905:Botulinum Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D001906:Botulism / Q000628:therapy; D015195:Drug Design; D006801:Humans
chemical_list: D000931:Antidotes; D001904:Botulinum Antitoxin; D001905:Botulinum Toxins