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The researchers identified a compound that strongly inhibits botulinum neurotoxin, the most toxic compound known. This inhibitory compound, nitrophenyl psoralen (NPP), could be used as a treatment to reduce botulism-induced paralysis. Botulinum neurotoxin is considered a potential biological weapon because there is no antidote approved by the FDA. The research is published in Applied and environmental microbiology, journal of the American Society for Microbiology.
As part of the study, the first step in the research was to identify the botulinum neurotoxin enzyme that damages neurons and causes paralysis. They then examined a library of more than 300 natural compounds extracted from Indian medicinal plant extracts, looking for enzymes that could neutralize the destructive activity of neurons.
"Using a high-throughput screening, we identified one of the compounds, nitrophenyl psoralen, as having a particularly strong activity against the destructive neuron enzyme," said the corresponding author, Bal Ram Singh, PhD, professor and director of the Botulinum Research Center of the Institute of Advanced Sciences. , Dartmouth, MA.
The researchers then tested MPP activity in vitro and in cell culture against botulinum neurotoxin type A, which is the most potent serotype of the seven serotypes of botulinum toxin. Type A nuclear power plants had potent anti-botulinum toxin activity, with low toxicity to human cells. (image: molecular model of botulinum neurotoxin)
"Nuclear power plants have also shown activity to reverse mouse muscle paralysis induced by botulinum neurotoxin type A," said Dr. Singh.
Although fewer than 200 cases of botulism occur each year worldwide, "they cost more to treat than the millions of salmonella outbreaks, making botulism the most expensive form of food poisoning", said Dr. Singh. Botulinum toxin is produced by Clostridium botulinum, a ubiquitous and hard-to-kill soil bacterium. Spores can survive cooking.
Botulism can be contracted by other routes than food poisoning, such as wound contamination and colonization of the digestive tract of children and infants.
Drugs derived from psoralen are already approved by the FDA in the United States. This would probably speed up the process of approving drugs for nuclear power plants, said Dr. Singh.
The research originated in Dr. Singh's group work on the biochemical basis of Ayurveda, a widely used herbal medicine system in India. Natural products, such as those used in Ayurveda, have more diverse structures, less toxicity and better drug properties than synthetic products. As founding director of the Center for Indic Studies at UMbad Dartmouth University, he considered natural herbal compounds as a source of countermeasures against botulism. This led to discussions and then to a collaboration on this work with Professor Virinder Parmar, head of the Department of Chemistry at the University of Delhi.
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Material provided by American Society of Microbiology. Note: Content can be changed for style and length.
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