What is Conotoxin?
The search for new & better drugs for treating infectious diseases, cancer & other ailments is never-ending. Most people are not aware that one of the richest sources of new drugs are of biological origin. This can include fungi, plants & surprisingly, a wide range of marine organisms. In this article, we describe one such drug, Ziconotide. It comes from the venom of the cone snail, Conus magus.
Ziconotide Treats Severe Chronic Pain
Opium derivatives, harvested from the poppy plant, are in the front line of pain management. Among them are familiar drugs such as morphine, heroin, oxycodone, hydromorphone & others. The problem is that many people adapt to these drugs in the late stages of cancer treatment. This makes severe pain very difficult to control.
Conopeptides (contoxins) are the venomous compounds of the marine snails, genus Conus sp. They are selective in the ion channels they block which makes them valuable potential candidates as novel painkilling drugs. Ziconotide (Prialt) is one such drug. It targets voltage-gated calcium channels associated with pain receptors & is estimated to be 1000 times more effective in treating intractable pain than morphine. Unfortunately, Ziconotide also has a downside. It can produce severe side effects when taken orally or intravenously. The safest option is direct injection into the spinal fluid.
Ziconotide: The Molecular Structure
The model shown below is one of the largest biological molecules we have done 3D Molecular Model Builder. The structure has 102 carbons & is distinguished by its 4 pairs of disulphide bridges created from the amino acid cysteine. (The video below predates the sale of our original domain from 1994, indigo.com).
Cone Snail Conus magus (Magic Cone)
The shells of these snails are 15-100mm long & are strikingly beautiful. Collectors prize them as highly valued as objets d’art. You can see the shell of Conus magus in section C of the image below, 2nd from the right.
Image courtesy of physrev.physiology.org/content/84/1/41.full
The Geographic Range of Conus magus.
The range of Conus magus is from tropical to subtropical from 40 degrees latitude north and south of the equator. It lives along the shores of Australia, the Philippines, India, Mexico & others.
Image courtesy: bioweb.uwlax.edu/bio203/2011/haas_kayl/Lagoon.htm
There are over 500 species in this genus, each with roughly 100 different toxins in their “arsenals”. These venoms have been adapted for prey animals including other snails, worms & even fish. Each venom is specific for receptor sites in prey species. The receptors in fish are very similar to those found in other vertebrates including mammals.
The snails deliver these venoms via an ingenious product of evolution. Most snails obtain nutrition by scraping off algae & other organic material from the surfaces they crawl over. Like all snails, Conus sp. feeds with a radula, essentially a tongue with teeth. These “teeth” have evolved into harpoon like structures that spear target prey & inject venom.
These snails are remarkable products of evolution & perfect examples of the need for preserving species diversity. They and many other species hold precious secrets we have yet to discover.
Cone snail “harpoons” are hollow and can inject venom into prey or human hands.
References
1) Cone snails general information: Wikipedia.
2) Ecological information: U. Wisconsin Lacrosse (link broken; removed).
3) Biochemistry & pharmacology information: Heinrich Terlau, Baldomero M. Olivera in Physiological Reviews 1 January 2004, Vol. 84 No. 1. (link broken; removed).
4) Ion channel general information. Wikipedia
