On the Molecular Dissection of Venom: Action and Antidotes

Abstract

Venom is a specialised weapon, a secretion that is actively delivered into anotherorganism, generally for predation or defence. It is a remarkable example of convergentevolution having appeared independently across many bacteria, plant, fungi, and animallineages. Interaction with venomous organisms affect millions of people annually resultingin significant morbidity, mortality, and associated economic burden. The advent of -omicstechnologies has allowed for great advances in the venom field. This includes whole-genome CRISPR screening approaches to look at how venoms act from the hostperspective. Using this technology, we surveyed a wide variety of snakes and otherorganisms and uncovered genes and pathways that are newly implicated in venom action.We also discovered that venom from Spitting Cobras (Naja pallida and Naja nigricollis),the Australian bluebottle jellyfish (Physalia utriculus), and the Atlantic Sea Nettle jellyfish(Chrysaora quinquecirrha) all require the heparan/heparin proteoglycan biosynthesispathway to cause cell death. These findings were confirmed genetically andpharmacologically and the results used to predict new drugs that could act as venomantidotes. The heparinoid drug class was observed to have broad anti venom activity andcould have translational promise for preventing the dermonecrosis seen in cobra bites andthe pain associated with jellyfish envenoming. We reason that as venoms need to hijackthe physiological pathways of host cells, diverse venoms utilise overlapping strategies togain cell entry or cause damage. By providing fundamental new insight into venom actionand helping us develop broad spectrum antidotes for medically relevant and painfulvenoms, the incorporation of functional genomics and CRISPR screens is an importantaddition to the “venomics” arsenal.