Envenomings by snakebites constitute a serious and challenging global health issue. The mainstay in the therapy of snakebite envenomings is the parenteral administration of animal-derived antivenoms. Significantly, antivenoms are only partially effective in the control of local tissue damage. A novel approach to mitigate the progression of local tissue damage that could complement the antivenom therapy of envenomings is proposed. We describe an abiotic hydrogel nanoparticle engineered to bind to and modulate the activity of a diverse array of PLA2 and 3FTX isoforms found in Elapidae snake venoms. These two families of protein toxins share features that are associated with their common (membrane) targets, allowing for nanoparticle sequestration by a mechanism that differs from immunological (epitope) selection. The nanoparticles are non-toxic in mice and inhibit dose-dependently the dermonecrotic activity of Naja nigricollis venom.

Author summary

Snake envenoming affects approximately 2.5 million people and causes more than 100,000 deaths annually. The WHO includes envenoming as a category A Neglected Tropical Disease. Therapy involves intravenous delivery of animal-derived antivenoms, constituted by IgG from the plasma of mammals immunized with venom. Antivenoms are species-specific, expensive and suffer the limitations of a biological therapy. There are no broad-spectrum antivenoms. The work describes hope for treatment of snakebite, a broad-spectrum antivenom comprised polymer nanoparticles (NPs) engineered to sequester the major protein toxins in elapid snakes. The stable, low-cost NPs can be administered subcutaneously immediately after the bite at the site of envenoming to halt or reduce the extent of local tissue damage and mitigate the systemic distribution of toxins post-envenoming.