Previously neglected venoms promise new drug targets
Powerful new research techniques illuminate the possibilities in 220,000 venomous species. Tanya Loos reports.
Venoms contain powerful proteins with fast acting precision and a wide range of devastating effects, but only six venom-based drugs have been developed to date.
A review published in the journal Science suggests this may be about to change, because the venoms of animals are now better studied and understood due to advances in the rapidly developing biological fields known collectively as the “omics”: genomics, proteomics and transcriptomics.
The first studies the entire genome, the second looks at proteins, and the last tackles the study of RNA molecules. All of these cellular level studies have provided researchers with new perspectives on the evolutionary history of venom, venom diversity and pharmacology.
The techniques have also enabled researchers to expand beyond the traditionally studied venomous creatures, such as spiders, snakes, scorpions and cone snails, to those that are small, rare or difficult to study in the lab.
There are over 220,000 described species of animal with venom – suggesting potential for the development of therapeutic compounds is huge.
“An evolutionarily informed perspective will help us focus venom research to leverage the extraordinary biochemical warfare nature has created,” says lead author Mande Holford, from Hunter College and City University of New York Graduate Centre, both in the US.
For example, detailed studies of the cnidarians, the diverse jellyfish and coral group, have forced a rethink of some commonly held ideas of venom evolution. The cnidarians were the first animal lineage to develop venom, some 500 million years ago, and their evolutionary biology is quite different to the so-called new venoms of snakes and cone shells, which are relatively young in an evolutionary sense, and still undergoing strong diversifying selection.
Recent research reveals that centipede venom has developed and diversified with convergent recruitment of toxin genes, and Holford says this shows the “the multiplicity of processes by which venom toxins arise and diversify even within a single lineage”. Some species, such as the assassin bug (from the family Reduviidae), even have two kinds of venom, one to subdue prey, and one to protect themselves from predators.
The evolutionary arms race between predator and prey has led to the development of extraordinarily precise compounds, making them ideal candidates for therapeutics. A drug based on an antidiabetic peptide in the venom of the Gila Monster (Heloderma suspectum) has been approved by the US Food and Drug Administration.
Venoms themselves are also proving an excellent tool with which to study ion channels and receptors, groups of cells which are involved in many essential physiological processes from breathing to seeing, or feeling pain.
For example, tarantula venom is being used to study the actions of specific pathways in sodium channels related to the nerves in conditions such as irritable bowel syndrome.
The authors, from institutions in the US and Australia, say there is a lot of work ahead. The research, they suggest, on previously neglected venomous species will reveal new molecules with novel mechanisms of action.
“A major challenge facing this emerging field will be the development of new computational methods for modelling the interaction of toxins and their molecular targets,” the paper concludes.