Poison: What better way to combine a love of reptiles, pharmacognosy, and biotechnology? Poisonous organisms and the toxic effect of their venom have long been objects of both fear and fascination. The evolution of venom systems is remarkably poorly understood despite their biological uniqueness and medical importance. Venom systems are key evolutionary innovations in a broad phylogenetic range of animal lineages and are used for defense, competitor deterrence, and predation.
Owing to their worldwide distribution, reptiles are among the most familiar venomous animals, but numerous other organisms on land and sea are equipped with venomous fangs, spines, barbs, or tentacles for the purposes of aggression, defense, or digestion. In addition to the extensively studied, medically-important classes (snakes, scorpions, and spiders), venomous animals include sea anemones, jellyfish, sea snails, cephalopods, centipedes, several insect orders, echinoderms, fish, lizards, and even some mammals (lorises, platypuses, and shrews). Targets of venom action include virtually all major physiological pathways and tissue types accessible by the bloodstream. Venoms of snakes contain at least 25 enzymes, inorganic substances, and small amounts of metal. In most species, the most lethal component of the venom is a peptide constituent. Some of the more important enzymes of reptiles include: proteolytic enzymes, phosphomonoesterase, arginine ester hydrolase, phosphodiesterase, thrombinlike enzyme, acetylcholinesterase, collagenase, RNase/DNase, hyaluronidase, 5’-Nucleotidase, L-Amino acid oxidase, and many more. Such enzymes catalyze the breakdown of tissue proteins and peptides but the pharmaceutical/toxicologic properties of many of these enzymes have not been well characterized.
- Antvenin (Antivenom) Immunotherapy: A serum composed of purified antibodies that is commercially produced to neutralize the effects of evenomation.
- Integrilin: A cyclic heptapeptide derived from a protein in the venom of the pygmy rattlesnake. The product was launched by Schering Plough in 1998 and approved for anticoagulation in patients with Acute Coronary Syndrome.
- Exendin-4: A peptide initially derived from the salivary secretions of the Gila monster (picture). In 1982, it was observed that the crude venom of the Gila monster (Heloderma suspectum) was a potent pancreatic secretagogue. Purification and sequencing of the active factors mediating this effect led to the discovery of the peptide exendin-4, a 390amino acid GLP-1 receptor agonist sharing ~53% homology with native GLP-1 and VIP. This peptide possesses glucoregulatory actions similar to GLP-1 and is resistant to degradation activity of DPP-IV because of a different amino acid sequence. The result is longer duration of action in vivo compared to native GLP-Byetta (exenatide) is used to treat type 2 diabetes.
Other areas of research on applying venom therapeutically include: analgesia, cancer, neurological disorders, and inflammatory diseases.
The nature we occasionally fear continues to provide inspiration and aid to drug developers, who, even with the advent of new technologies, cannot match its complexity and diversity.