Cnidarian Venoms in the Omics Era: Toxin Discovery and Bioactive Potential

Cnidaria is a phylum of aquatic invertebrates that includes jellyfish, sea anemones and corals. Their venoms are among the oldest in the animal kingdom and an important source of bioactive molecules. Advances in omics technologies have revolutionized toxin discovery, yet knowledge of cnidarian toxin diversity remains fragmented across databases and individual studies. To address this gap, this review integrates information from 342 toxins curated in the ToxProt database, 76 additional toxins reported in the literature, and evidence from 81 proteomic and 31 transcriptomic studies. Toxins have been characterized from 145 species, with sea anemones accounting for the largest number of studied species (65). Cnidarian toxins are used for prey capture, predator deterrence, territorial competition and digestion. These include toxic enzymes, neurotoxins, protease inhibitors and pore-forming toxins, among others. To date, the three-dimensional structures of 37 toxins have been resolved, and 78 have reported biomedical or biotechnological potential, including antiarrhythmic, analgesic, anticancer, and insecticidal activities. According to omics studies, metalloproteinases, phospholipases, lectins, Kunitz-like peptides, venom coagulation factor and CRiSP/CAP toxins are the most widespread, whereas neurotoxins show a more restricted taxonomic distribution. The first venom-related transcriptomic analysis of three Corallimorpharia and two Antipatharia (black corals) species demonstrates putative pore-forming toxins, while black corals also harbor putative neurotoxins. Overall, this review synthesizes the current knowledge of cnidarian venoms and highlights their remarkable diversity and promise as a source of bioactive molecules.