A Natural Compound Isolated from an Indian Medicinal Plant Inhibits the Action of Botulinium Neurotoxin

The neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinium are amongst the most poisonous proteins known. These toxins block neurotransmitter release by cleaving N- ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, inducing paralysis. In a recent study published in Applied and Environmental Microbiology,1 300 natural compounds isolated from a panel of Indian medicinal plants were screened by biochemical and cellular assays for the ability to antagonise the catalytic active site of BoNT, thereby inhibiting the activity of the protein. Nitrophenyl psoralen (NPP) was identified as a potent inhibitor of BoNT activity, with an IC50 of <4 μM. Furthermore, NPP can also reverse BoNT associated muscle paralysis in a murine model and have low toxicity in humans. Indeed, multiple psoralen derivative drugs are already approved by the US FDA, thereby potentially simplifying the drug approval process for NPP.