title: 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.
authors.affiliation: Microbiotix, Inc., One Innovation Drive, Worcester, MA 01605, USA. bli@microbiotix.com
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Norton P
authors.initials: NP
authors.lastname: Peet
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Butler
authors.forename: James C
authors.initials: JC
authors.lastname: Burnett
authors.forename: Donald T
authors.initials: DT
authors.lastname: Moir
authors.forename: Terry L
authors.initials: TL
authors.lastname: Bowlin
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001905:Botulinum Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D018360:Crystallography, X-Ray; D005089:Exocytosis; D006801:Humans; D008958:Models, Molecular; D009469:Neuromuscular Junction / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D001905:Botulinum Toxins; D000109:Acetylcholine