One of the world’s most poisonous creatures could serve as inspiration for drugs to treat diseases that affect hundreds of millions of people, according to a new study.
Led by researchers at the University of Utah, scientists have discovered a component in the venom of a sea snail that mimics an important human hormone involved in regulating blood sugar and hormone levels.
The results published in the journal Nature communicationdescribe in detail how a venom from the geographic cone snail called consomatin behaves similarly to somatostatin, a hormone responsible for regulating blood sugar levels and several other hormones.
Geography cones are a species of predatory sea snail typically found in reefs in the tropical Indo-Pacific and are known to hunt small fish.
Safavi Laboratory
It is the most poisonous of the known cone snail species. According to a study published in the Journal of the American Journal of Medicine, almost all human deaths caused by cone snails are attributed to them. International Journal of Clinical Pharmacology and Therapeutics.
But its deadly toxin, if isolated, could have pharmaceutical potential. Unlike the natural human hormone somatostatin, consomatin is more stable and precise, making it a promising candidate for drug development.
“Human somatostatin binds to five different membrane receptors, triggering a variety of physiological actions,” said Ho Yan Yeung, lead author and postdoctoral fellow at the University of Utah. Newsweek“However, the cone snail’s somatostatin-like toxin only binds to one of the five membrane receptors to exert its targeted effect.”
The cone snail uses consomatine to paralyze its prey by preventing the rise in blood sugar levels – a mechanism that is lethal to fish. The researchers believe this property could also help develop better drugs for people with diabetes and hormone disorders.
Synthetic drugs that regulate hormone levels are currently important therapies, but they can have side effects. Consomatine’s targeted action could allow chemists to develop more effective treatments with fewer unintended consequences.
“We’ve been trying to do medicinal chemistry and drug development for a few hundred years, sometimes with poor results,” Helena Safavi, associate professor of biochemistry at the University of Utah and lead author of the study, said in a statement. “Cone snails have had plenty of time to do it really well.”
Safavi Laboratory
And the cone snail’s venom is even more sophisticated than previously thought. The research team had already identified another venom component that mimics insulin and rapidly lowers the blood sugar levels of the snail’s prey. Together, these toxins lower blood sugar levels to dangerously low levels and keep them there, rendering the prey unresponsive.
“This paper essentially shows that our initial discovery of venom insulin is not an outlier of venom peptides that mimic hormonal effects,” said Danny Hung-Chieh Chou, associate professor of pediatric endocrinology at Stanford University. News week. Chou worked with Safavi on the insulin mimicking study but is independent of that study.
“Instead, there may be many more waiting to be discovered, and these could potentially be life-saving therapies,” he said.
Safavi Laboratory
Researcher Yeung agrees, explaining in a press release: “This means that the venom may not only contain insulin and somatostatin-like toxins. It may also contain other toxins that regulate blood sugar levels.”
However, one should not expect consomatine-based medications to appear on the shelves any time soon.
“Due to its strong effect on suppressing the blood sugar-lowering hormone glucagon, especially in combination with insulin, we believe there is a risk of hypoglycemia,” Yeung said.
Instead, by studying the structure, the team hopes to discover other compounds that could work in a similar way to treat diseases related to hormone imbalances.
In addition, Yeung and team are investigating the therapeutic potential of cone snail toxins for use in pain management and metabolic disorders.
“The venom of cone snails or other poisonous animals offers so many interesting inspirations for the development of new drugs that have yet to be discovered,” she said.
While it may seem odd to choose a deadly snail for medical innovation, the research underscores that evolution has perfected mechanisms that scientists can now repurpose to benefit humanity.
“Cone snails are just really good chemists,” Yeung said.
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References
Kohn AJ. Human injuries and deaths caused by venomous marine snails of the family Conidae. Int J Clin Pharmacol Ther. 2016 Jul;54(7):524-38. doi: 10.5414/CP202630. PMID: 27285461.
Yeung, HY, Ramiro, IBL, Andersen, DB, Koch, TL, Hamilton, A., Bjørn-Yoshimoto, WE, Espino, S., Vakhrushev, SY, Pedersen, KB, de Haan, N., Hipgrave Ederveen, AL, Olivera, BM, Knudsen, JG, Bräuner-Osborne, H., Schjoldager, KT, Holst, JJ, & Safavi-Hemami, H. (2024). Fish-hunting cone snail disrupts prey glucose homeostasis with weaponized mimics of somatostatin and insulin. Nature communication, 15(1), 6408. https://doi.org/10.1038/s41467-024-50470-2
Xiong, X., Menting, JG, Disotuar, MM, Smith, NA, Delaine, CA, Ghabash, G., Agrawal, R., Wang, X., He, X., Fisher, SJ, MacRaild, CA, Norton, RS, Gajewiak, J., Forbes, BE, Smith, BJ, Safavi-Hemami, H., Olivera, B., Lawrence, MC, & Chou, DH-C. (2020). A structurally minimized yet fully effective insulin based on the principles of cone snail venom insulin. Nature Structural and Molecular Biology, 27(7), 615-624. https://doi.org/10.1038/s41594-020-0430-8
