Identification of 3-hydroxy-1,2-dimethylpyridine-4(1)-thione as a metal-binding motif for the inhibition of botulinum neurotoxin A.

Botulinum neurotoxin serotype A (BoNT/A) is an important therapeutic target owing to its extremely potent nature, but also has potential use as a biowarfare agent. Currently, no therapeutic exists to reverse the long-lasting paralysis caused by BoNT/A. Herein, we describe the identification of 3-hydroxy-1,2-dimethylpyridine-4(1)-thione (3,4-HOPTO) as a metal binding warhead for the inhibition of BoNT/A1.