Broad-Spectrum Detoxification of Snake Venoms With Supramolecular Materials Integrated via Molecular Recognition and Coassembly

Snakebite is a medical emergency that often leads to high mortality and morbidity in tropical and subtropical regions. The diversity in venom composition between various types of snakes necessitates the use of different specific antivenom treatments, which presents clinical and financial challenges in the management of snakebites. Therefore, developing a broad-spectrum antidote to neutralize complex and diverse snake venoms has assumed critical importance. Herein, a broad-spectrum antidote is developed through molecular recognition and coassembly to neutralize four kinds of snake venom toxins, those are three-finger toxin (3FTx), snake venom metalloproteinase (SVMP), phospholipase A2 (PLA2), and snake venom serine protease (SVSP), which have high abundance and toxicity. The coassembly of sulfonate-modified amphiphilic calixarene (SCA) and amphiphilic cyclodextrin (CD) is employed to neutralize the toxicity of 3FTx, 1,2-dodecanedithiol (DDT) and thioetheramide phosphorylcholine (TEAPC) are introduced through coassembly to neutralize toxicity of SVMP and PLA2, respectively, and the nafamostat (NT), which can be loaded through the host-guest complexation, is employed to neutralize toxicity of SVSP. The broad-spectrum antidote, NT@SCA/CD/DDT/TEAPC, effectively neutralizes key toxins from the most medically important cobra and vipers, significantly improving survival rates of poisoned mice. This study conceptually validated the feasibility of broad-spectrum detoxification and also offers a conveniently integrated supramolecular strategy.