The marine cone snail (Conus araneos), endemic to the waters off India’s southeast coast and Sri Lanka, can pack a punch with its venom. The cone snail paralyses its prey, usually small fish, in an instant, using its harpoon-like teeth to inject a cocktail of poisonous protein pieces. It turns out that one of those pieces present in the venom can potentially put mammals gently to sleep for a few hours, opening up possibilities for its use in treating sleep disorders such as insomnia and apnoea. New research from India adds to currently known potential biomedical uses of this marine mollusc – from existing and potential painkillers to diabetes treatment.
The venom of the marine cone snails is just as diverse as the species is. The venom of each species contains over 1,000 different chemicals called conotoxins that form its deadly arsenal against prey.
A team from Indian Institute of Science, Bangalore, and Andaman and Nicobar Centre for Ocean Science and Technology extracted the venom from the glands of cone snails captured in crab nets from the Gulf of Mannar in Tamil Nadu. Then, they isolated 14 peptides, or protein pieces, composed of 20 to 30 amino acids, which are the building blocks of proteins. Finally, the scientists genetically sequenced and classified the peptides and zeroed in on five to check for their biological activity in mice.
Of the five, one that they dubbed ‘ar3j’ showed signs of effect on mice: it caused the rodents to fall asleep within four minutes of being injected, they slept for two hours. When the scientists increased the dosage by about 2.5 times, the mice slept longer, for five hours, but also took a longer time – 10 minutes – to fall asleep as well as to regain their normal levels of activity.
This is the first report of a peptide from a cone snail that induces sleep in mice, the scientists’ report in the journal Toxicon (paywall) says.
Nonetheless, they are yet to pin down the exact chemicals that induce the stupor. “We have found the peptide responsible for sleep in mice,” said Jayaseelan Benjamin Franklin, scientist at the Andaman and Nicobar Centre and lead author of the study, to The Wire. “However, we are still working towards to find the exact mechanism. Once we find the mechanism, we will proceed for drug development.” Only a few herbs and few cone snails have such properties, he added.
Currently, several drugs obtained from Conus toxins are in use or are used in clinical trials as non-addictive painkillers in cancer and neuroscience research.
In January 2015, scientists from the University of Utah, Salt Lake City, led by Helena Safavi-Hemami, reported in the Proceedings of National Academy of Sciences that two cone snails – C. geographica and C. tulipa – also contain an unusual insulin-like substance in the venom, which results in a hypoglycaemic shock induced by extremely low blood sugar levels. Normally, insulin helps remove excess sugar levels, but an excess of the hormone can cause sugar levels to drop to a point that causes disorientation, and eventual loss of consciousness and death. The cone snail sprays its unique insulin – a far smaller molecule compared to the one used to reduce blood sugar – to confuse its prey and send it into a coma, before striking.
According to the researchers, the cone snails’ fast-acting insulin molecule could help improve diabetes treatment.
Moreover, scientists from the University of Queensland, led by David Craik, reported developing at least five new potential painkillers using a peptide from cone snail venom. At a meeting of the American Chemical society in March 2014, Craik’s team reported that the five substances could be stronger than morphine and with few risks of addiction.
So far, the US Food and Drug Administration has already approved a painkiller called Prialt, which is one of the most effective drugs to treat chronic pain, and which is based on a piece of protein from a conotoxin of Conus magus. In the same vein, Franklin believes that other marine plants and animals, not just the cone snail, hold tremendous promise for developing new and better drugs.