Abstract
With the inclusion of snakebite envenoming on the World Health Organization’s list of Neglected Tropical Diseases, an incentive has been established to promote research and development effort in novel snakebite antivenom therapies. Various technological approaches are being pursued by different research groups, including the use of small molecule inhibitors against enzymatic toxins as well as peptide- and oligonucleotide-based aptamers and antibody-based biotherapeutics against both enzymatic and non-enzymatic toxins. In this article, the most recent advances in these fields are presented, and the advantages, disadvantages, and feasibility of using different toxin-neutralizing molecules are reviewed. Particular focus within small molecules is directed towards the inhibitors varespladib, batimastat, and marimastat, while in the field of antibody-based therapies, novel recombinant polyclonal plantivenom technology is discussed.
Highlights
Snakebite is an epidemic of the rural tropics, which annually affects over 5 million people [1]
Confronted with the severity of this neglected tropical disease through a campaign led by the Global Snakebite Initiative, Health Action International, Médecins Sans Frontières, the African Society of Venimology, and the Government of Costa Rica, the World Health Organization (WHO) reinstated snakebite envenoming on its list of Category A Neglected Tropical Diseases in 2017 [22,23,24,25] and set down a working group that will develop an official strategy for prevention and treatment of snakebite envenoming [26]
While improvements are needed to increase the plantivenom’s titer and neutralizing capacity of the coagulant activity of B. asper venom to become on par with existing antivenoms, this study clearly demonstrates promising results for a highly innovative approach to antivenom development
Summary
Snakebite is an epidemic of the rural tropics, which annually affects over 5 million people [1] This leads to 1.84 million cases of envenoming and upper death toll estimates of 94,000, experts generally agree that these numbers are likely underestimated [2]. Despite recent reports on innovative approaches for developing a new generation of antivenoms based on biotechnological methods, medicinal chemistry, and antibody technologies [17,18,19], plasma-derived antivenoms of animal origin remain the only effective treatment against snakebite envenoming [20,21]. With the renewed international focus on snakebite envenoming, we here provide an updated overview of the most recent advances in the development of next-generation antivenoms that are not based on conventional animal immunization schemes. This review focuses solely on developments reported after 2016, as earlier important examples have been reviewed extensively elsewhere [17,18]
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