Abstract
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.
Highlights
Envenomings by snakebites constitute a serious and challenging global health issue, which affects approximately 2.5 million people and causes more than 100,000 deaths annually
The World Health Organization (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
Summary
Envenomings by snakebites constitute a serious and challenging global health issue, which affects approximately 2.5 million people and causes more than 100,000 deaths annually. This situation is acute in impoverished rural settings of sub-Saharan Africa, Asia and Latin America [1,2,3,4]. The mainstay in the therapy of snakebite envenomings is the parenteral administration of animal-derived antivenoms, constituted by IgG or IgG fragments purified from the plasma of large animals immunized with venoms [6, 7]. When prepared by using appropriate mixtures of venoms for immunization and following Good Manufacturing Practices (GMPs), antivenoms are safe and effective drugs which, if administered timely, can control the main pathophysiological manifestations of envenomings, especially those associated with systemic effects [6, 7]
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