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Spiders, Venom, and Pain – Oh My!

Spiders, more specifically their venom, are the next enticing source of pharmaceuticals. Many of the peptides found in various species of spiders’ venom are pharmacologically active. We are acutely aware of the nasty neurotoxic effects but other components of venom demonstrate a variety of drug-like effects, including analgesic, antimicrobial, hemolytic, antiarrhythmic, and even enzyme inhibition. The possibilities for drug discovery are enormous.

Spiders are the most prevalent venomous species on the planet. Since most spider venoms are actually a complex mixture (a toxtail, if you will), of mostly peptides along with some other organic compounds. It is estimated that there could be over 12 million unique peptides produced by the venomous portion of our 100,000+ species. So far, we have just scratched the surface, with the latest total on the ArachnoServer listing over 1500 toxins from just 100 species. This database curates data from UniProt, a scientific consortium, with a mission to “provide the scientific community with a comprehensive, high-quality and freely accessible resource of protein sequence and functional information.” The ArachnoServer itself also uses the World Spider Catalog for its taxonomy identification. No mention of radioactice spiders here.

Most peptides do not make for good drugs because of their innate instability and limited human absorption. But here is where spider venom gets really cool. It turns out that in most spider toxins the biologically active peptide is “packaged” in what is called a “inhibitor cystine knot (ICK),” which essentially embrace the peptide to create a very stable mini-protein. Crazy shtuff. Without getting too deep into this science, suffice it to say that new studies are looking at oral dosage forms for humans. The ICK peptides are resistant to pH extremes, proteolytic enzymes, and high temperatures.

The most exciting area of spider venom research is in the area of treatment of chronic pain. In light of our current opioid dilemma, the possibility that we could have a non-addictive pain reliever is exciting. Our growing knowledge of certain neural ion channels playing a role in the inception and perception of pain, coupled with our growing knowledge of these spider peptides, may lead to some new effective remedies. A group of researchers in Australia is studying the peptide toxin – known as ProTx-II – that inhibits pain signals by binding to the membranes of nerve cells. This toxin is found in the venom of the Green Velvet Tarantula.

We already have pharmaceuticals derived from venom found in the animal kingdom. Pharmacists will know the drug the venom-derived drug approved by the FDA, exenatide (a glucagon-like peptide-1 agonist), which helps treat type 2 diabetes. It was originally isolated from the saliva of the Gila monster, a venomous lizard.

There is a pretty good article from the British Journal of Pain here at the NIH.

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2 Comments

  1. Very interesting. Captopril is another example of snake venom being developed into a human medication. The Brazilian (bothrops) jararaca was noted to drop a man on the spot due to a sudden, severe bp decrease. Venom is fascinating.

    • Good point. Captopril was our introduction to the role of angiotensin converting enzyme (ACE) inhibitors in regulating blood pressure. The pit viper was a great help to medicine!

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