Research advances in inhibitors of botulinum neurotoxins

Abstract:

Botulinum neurotoxins (BoNTs) secreted by Clostridium are the most toxic biotoxins known.BoNTs are classified into seven serotypes (BoNT/A-G),of which BoNT/A is the most frequent cause of botulism.Due to the strong toxicity and easy preparation,BoNTs are classified as the class A bioterrorism agents.At present,botulism is mainly treated by early administration of antibotulinum serum.However,the antibotulinum serum has limited effect and cannot reverse the paralysis caused by botulism when the toxin enters nerve cells.Therefore,it is necessary to develop more effective drugs for treating botulism.Because small-molecule inhibitors can overcome the limitation that antitoxin cannot neutralize intracellular toxins,they have become a popular direction in the development of novel drugs for treating botulism in the past decades.As the structure of BoNTs and the mechanism of botulism have been gradually elucidated,more and more relevant targets are being used to develop effective inhibitors.This paper reviewed small-molecule inhibitors of BoNTs in recent years according to their mechanisms.