New potentially painkilling compound found in deep-water cone snails

The venom of cone snails can be used to treat chronic pain, diabetes and other human diseases. There are more secrets to be revealed about the cone snails venom. A group of cone snails produce a venom compound similar to the hormone somatostatin, according to a new study.

The results show the wide variety of drug leads that venomous animals produce, designed and refined over millions of years.

"We have to broaden the scope of what we expect that these venomous animals make, assuming that they could really be making anything," says a professor at the University of Utah.

"Cone snail venom is like a natural library of compounds, it is just a matter of finding what is in that library", says Iris Bea Ramiro of the University of Copenhagen.

Beginning in the province of Bohol.

The story begins in the Philippines, where Ramiro was born. Although she and most of the people in the province didn't see cone snails often, fishermen knew how to find and catch them. Ramiro was told by a fisherman that his parents warned him not to eat the snail's bean-like organ.

Ramiro says that the bean-like structure is a bulb that is connected to the glands where venom is produced.

Some cone snails are hunters. Some of those use a stun-and-tether hunting strategy, shooting a barbed hook into a fish, and delivering a shock of venom that paralyzes the fish. Others use a net hunting strategy, releasing a cloud of venom into the water with compounds that leave the fish sensory-deprived and confused.

Half of the groups of fish hunting cone snails have been studied. The Asprella cone snails are not studied very much. They are not shallow-water snails. They like deeper waters and have been less accessible to scientists.

Ramiro was a graduate student at the University of the Philippines when she began studying Conus rolani.

She found one. The mice acted sluggishly or unresponsive because of the smallpeptide from the venom. Since other cone snails produce venoms that act almost immediately, it was not expected that it would take SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA SALVAGEDATA It had some similarities to the hormone somatostatin, but not enough to say that the venom and human hormones were functionally related.

Ramiro went to the University of Utah to investigate how and why the venom worked.

The snails are at the U.

Since 1970, when Baldomero "Toto" Olivera arrived in Salt Lake City, U researchers have been studying cone snails and their venom.

The venoms interact with the bodies of prey fish and overwhelm the body's natural biochemical processes, thanks to decades of study. Olivera and his colleagues looked into whether those effects could be used as pharmaceuticals. One attempt yielded a pain medication. In one of the studies, Safavi was an assistant professor and investigated how cone snails might be used to make a fast-acting type 2 diabetes drug.

Cone snails take some of their hormones and turn them into weapons. She and other researchers helped Ramiro compare Consomatin Ro1 to known human proteins.

X-ray crystallography was used to determine the structure of Consomatin Ro1, and it showed that it does not resemble somatostatin.

The research team worked with local fishermen off the coast of the island of Cebu to bring samples to the lab to learn more about their biology.

Ramiro says it took a year to confirm that the somatostatin that she isolated from the C. rolani snail activated two of the five human receptors.

We really wanted to understand what it was doing and how it could be better than somatostatin.

There are snakes and snails.

Somatostatin is a hormone that is found in humans and many other animals. It can be used to treat excessive growth disorder acromegaly. hormones in the pancreas and signals of pain and inflammation are some of the things it does.

The human body has many, many different functions and this hormone is always blocking them. It was an interesting hormone for drug development because of that.

How can a hormone like somatostatin work when it acts slowly? The best way to understand that is to look at the rattlesnake.

Rattlesnakes, vipers and cobras have developed a hunting strategy to protect themselves against dangerous prey. The snakes strike and then retreat. They wait for the venom to kill their prey and then follow them until they can approach and eat them.

There were similarities between the strike-and-release hunting strategy of the rattlesnake and the cone snails. The snails would wait up to three hours before delivering a second injection.

When the prey is unable to swim, they come and eat it. That is important if the prey can fight back.

How does a venom component help with that strategy? It is still unclear. According to the study, Consomatin Ro1 can block pain in mice with efficiency similar to morphine, and it may be used to block pain so that prey doesn't know it's been struck. Different species of fish hunters use different toxins.

Drug designers are tiny.

As a somatostatin analog, Consomatin Ro1 is structured as if it was designed by drug makers.

That is likely a reflection of evolution. Cone snails probably began using their own somatostatin in venom and refined the compound for maximum effectiveness through generations of trial and error. Since the biology of fish and humans is similar, a compound that is highly effective in fish will likely be effective in humans.

It is not yet known if Consomatin Ro1 is more effective than somatostatin analog drugs already on the market that treat growth disorders or tumors.

There are many species of cone snails and the chances of finding the best one are high.

Future directions.

The research team wants to better understand the potential of Consomatin Ro1 as an anti-Inflammatory or Pain Relief, as well as the origin of the compound in snails. Modifications to the compound could make it even more useful.

The results show how venomous animals can turn a hormone into a weapon and suggest that the range of biochemical tools in venom might be broader than previously thought.

There is evidence that hormones can be turned into weapons by viruses. If we did the latter, we might be more successful or we might be quicker in our drug development efforts.

This shows how evolution in the natural world has already developed drug-like natural products that have great potential to improve human health.

Ramiro says that discovering new peptides from the cone snails is fun and exciting, but it could be a long and difficult journey.

More information: Iris Bea L. Ramiro et al, Somatostatin venom analogs evolved by fish-hunting cone snails: From prey capture behavior to identifying drug leads, Science Advances (2022). DOI: 10.1126/sciadv.abk1410. www.science.org/doi/10.1126/sciadv.abk1410 Journal information: Science Advances Citation: New potentially painkilling compound found in deep-water cone snails (2022, March 23) retrieved 23 March 2022 from https://phys.org/news/2022-03-potentially-painkilling-compound-deep-water-cone.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.