RESUMEN
Botulinum neurotoxins (BoNTs) are the most deadly biological substances, including seven BoNT serotypes (A-G), and characterized by persistent flaccid paralysis of peripheral never terminals with high specificity called botulism. Due to their easy production and well-defined biological mechanism, BoNTs are wildly used in cosmetics and as very particular biopharmaceuticals in clinical therapy, so there is the risk of poisoning caused by accidental overdose. Also, because of their high toxicity, they are potential bioterrorism weapons. Thus, there is an urgent need for the development of BoNT inhibitors. In this review, based on the structure of BoNTs and the mechanism of botulism, we summarize recent advances in small molecule inhibitors targeting the Zn2+ active site of BoNT/A, such as 8-hydroxyquinoline and hydroxamic acid, or exosite of BoNT/A, small molecule inhibitors of BoNT/A through covalent binding that are irreversible, as well as small molecule inhibitors of targeting BoNT/B/ E light chain (LC).