The Functional Activity of Procoagulant Snake Venoms and Their Paraspecific Neutralisation by Antive

Ainsworth, Stuart

Slagboom, Julien

Casewell, Nicholas R.

Alistair Reid Venom Research Unit

Parasitology Department

Liverpool School of Tropical Medicine

Pembroke Place

Liverpool, L3 5QA, UK

Snakebite causes over 100,000 deaths each year, making it one of the world's most neglected tropical diseases. The specific pathologies resulting from envenoming are dictated by the toxin composition of venom, which varies by species, geography and ontogeny. Such extensive toxin variation severely restricts the paraspecific efficacy of antivenom therapies used to treat snakebite victims, as the active immunoglobulins are limited to neutralising only those venom toxins present in the immunising mixture. With a view to devising new types of ‘pathology-specific’ snakebite treatments with global, rather than geographically restricted, efficacy, we characterised the coagulopathic nature of a variety of snake venoms via their interaction with different targets in the blood clotting cascade. Different snake venoms act on Factor X, prothrombin and/or fibrinogen in a variable manner to initiate consumption coagulopathy, which is one of the most common medically-important pathologies observed following snakebite. Despite the variability in functional targets, we find that a number of existing antivenoms exhibit surprisingly high levels of cross-neutralisation against procoagulant venoms in vitro and in vivo, seemingly due to the convergent evolution of similar venom toxin profiles in different snake species. These results hold much promise for the future design of targeted toxin-specific antibodies to treat pathologies caused by envenoming, irrespective of the snake species responsible.