In the wild, survival of the fittest for some plants and animals mean sporting lethal venoms and toxins to kill whatever bothers it. But ironically enough, the chemical properties that make these natural toxins so deadly are also what make it so valuable as medical cures. The catch, of course, is to extract the curative properties without the dangerous lethal side-effects. Now a team from the Scripps Research Institute say they have found a way to screen more toxins
for therapeutic properties faster and more efficiently. Their system, they say, could reveal more drugs currently hiding inside of snake venom, frog poisons, and the likes.
Nature’s own toxins are exquisitely efficient at killing. Some of these toxic concoctions of proteins and peptides target the nervous system, causing death by paralysis. Some dissolve cells and tissues, causing death from the inside out. Some coagulate blood into the consistency of gelatin, turning the victim into a macabre human Jell-o mold.??
But where’s the medicinal value of these compounds? As it turns out, some of the most active components of toxins affect the same enzymes and pathways in certain diseases. Deriving the key active ingredients from the toxins could yield huge therapeutic potentials. Aside from yielding the key chemical compound, toxins also lead scientists to better understand how certain diseases work, what pathways are affected, and what proteins may be curative. ??
So far, toxicologists are hard at work screening natural toxins for medicinal values. Of the possible 20 million toxins in nature, less than a 1,000 have been analyzed. And of that, only about a dozen have made it as a marketable drug. The process is so lengthy because it’s highly difficult to obtain sufficient quantities of the poisons or venoms naturally. In addition, once isolated, the compound has to be purified and tested in a multitude of lab conditions to see how cells respond.
Recognizing the vast potential of drugs that are yet undiscovered in natural toxins, the team at Scripps set to find a new way to screen for these drugs in a more efficient manner.
They began by assembling a list of 589 known venoms (using an animal toxin database). From this, they synthesized gene versions for each of the venoms, and inserted the gene into viruses that deliver the genes into cells. The next step is to test whether the genes have a biological effect by exposing the virus to cultured cells that have a reporter, such as a fluorescent signal, attached. When a biological target is affected by the right gene from the venom, the cells light up and alerts researchers to hone in on a particular venom.
As a proof-of-concept, the team screened for venoms that block a potassium ion channel known as Kv1.3. This channel, in particular, is involved in many biological processes, including inflammation and disease.
Using their screening technique, the team narrowed down the daunting list of 589 candidate venoms to just 27 that most likely blocked Kv1.3. Of this 27, 25 venoms have already been validated as targeting the potassium channel, indicating that the technique is effective. Of the 2 venoms that are previously unknown, one had been suspected to be involved in Kv1.3 block, and the other was verified with actual venom to be a potent Kv1.3 blocker.
The team hopes this method will be effective for drug discovery not only with natural toxins, but also in identifying analog versions of these compounds.
Additional source: EurekAlert!