Animal toxins in drug discovery
Spiders, scorpions and insects as well as some marine animals produce venoms. Given their high and complex content of peptides, venoms are increasingly being considered for their potential therapeutic use. Commercially available drugs already exist for alleviating pain in HIV and blood coagulation and are mostly based on snake and cone snail venom peptides. Currently, the pharmaceutical industry is investing more and more in venom-based drugs. To study the diversity and pharmacology of venom peptides, scientists on the EU-funded VENOMICS (High-throughput peptidomics and transcriptomics of animal venoms for discovery of novel therapeutic peptides and innovative drug development) project have generated the largest synthetic peptide library worldwide. Out of a total of 170 000 venomous animals, consortium partners combined proteomics, performed on venoms, and transcriptomics, performed on venom glands, extracted from more than 200 species. The researchers generated a high-throughput workflow based on the largest collection of venom and tissue samples ever studied. The idea was to identify all the toxins expressed in venom glands and characterise peptide maturation occurring in the venom. In turn, this enabled the generation of 25 000 toxin sequences. From these, more than 3 600 most interesting sequences are set for production by chemical synthesis or recombinant expression. Validation of both the approach and the selected peptides as drug candidates will be performed in functional and receptor-targeted assays specifically linked to age-related pathologies. VENOMICS has opened a new avenue in venom exploration and exploitation with the development of unique technologies without any limitation issues associated with the availability of natural products. Dissemination included 7 scientific papers, 3 press events Europe-wide, 11 articles in newspapers and 124 publications online, as well as TV and radio, the latest being Euronews. The study has generated libraries that will feed into the drug pipeline, and the VENOMICS drug discovery approach could offer innovative drugs as novel treatments. Screening of these toxins against therapeutic targets related with allergies, diabetes, autoimmune diseases and inflammation enabled identification of active drug candidates.
Keywords
Animal toxins, drug discovery, venom, high-throughput, VENOMICS, drug development
