Vipers, mambas and taipans: the escalating health crisis over snakebites

Arnold, Carrie

doi:10.1038/537026a

Cited by 34 publications

(18 citation statements)

References 5 publications

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“…Despite this, snakebite receives little attention from global health agencies, charities or governments, perhaps best exemplified by the World Health Organization (WHO) currently omitting snakebite from their formal list of neglected tropical diseases (http://www.who.int/neglected_diseases/diseases/en/). Despite this, the snakebite community continues to lobby for greater recognition surrounding this issue (Williams, ; Arnold, ), and recent progress has led to the WHO formally considering recognising snakebite as a neglected tropical disease at the upcoming World Health Assembly in 2017 (Harrison & Gutiérrez, ).…”

Section: Snakebite Is a Neglected Tropical Diseasementioning

confidence: 99%

Haemotoxic snake venoms: their functional activity, impact on snakebite victims and pharmaceutical promise

et al. 2017

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SummarySnake venoms are mixtures of numerous proteinacious components that exert diverse functional activities on a variety of physiological targets. Because the toxic constituents found in venom vary from species to species, snakebite victims can present with a variety of life‐threatening pathologies related to the neurotoxic, cytotoxic and haemotoxic effects of venom. Of the 1·8 million people envenomed by snakes every year, up to 125 000 die, while hundreds of thousands survive only to suffer with life‐changing long‐term morbidity. Consequently, snakebite is one of the world's most severe neglected tropical diseases. Many snake venoms exhibit strong haemotoxic properties by interfering with blood pressure, clotting factors and platelets, and by directly causing haemorrhage. In this review we provide an overview of the functional activities of haemotoxic venom proteins, the pathologies they cause in snakebite victims and how their exquisite selectivity and potency make them amenable for use as therapeutic and diagnostic tools relevant for human medicine.

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Section: Snakebite Is a Neglected Tropical Diseasementioning

confidence: 99%

Haemotoxic snake venoms: their functional activity, impact on snakebite victims and pharmaceutical promise

et al. 2017

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“…Toxins 2017, 9,158 5 of 12 kg humans, and against which the antivenom is not effective. Clearly, clinical studies are required to determine the effectiveness of EchiTAb-Plus-ICP ® against envenomings by N. melanoleuca.…”

Section: Toxicovenomics-guided Toxin-resolved Antivenomics Predictionsmentioning

confidence: 99%

Third generation antivenomics: Pushing the limits of the in vitro preclinical assessment of antivenoms

Plá

Rodríguez

Calvete

2018

Toxicon

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Second generation antivenomics is a translational venomics approach designed to complement in vivo preclinical neutralization assays. It provides qualitative and quantitative information on the set of homologous and heterologous venom proteins presenting antivenom-recognized epitopes and those exhibiting impaired immunoreactivity. In a situation of worrying antivenom shortage in many tropical and sub-tropical regions with high snakebite mortality and morbidity rates, such knowledge has the potential to facilitate the optimal deployment of currently existing antivenoms and to aid in the rational design of novel broad specificity antidotes. The aim of the present work was to expand the analytical capability of the immunoaffinity second-generation antivenomics platform, endowing it with the ability to determine the maximal binding capacity of an antivenom toward the different toxins present in a venom, and to quantify the fraction of venom-specific antibodies present in a given antivenom. The application of this new platform, termed third generation (3G) antivenomics, in the preclinical evaluation of antivenoms is illustrated in this paper for the case of antivenom EchiTAb-Plus-ICP ® reactivity towards the toxins of homologous (B. arietans) and heterologous (N. melanoleuca) venoms.Toxins 2017, 9, 158 2 of 12 launch by the WHO of a prequalification scheme of antivenoms for sub-Saharan Africa, a programme also supported by the Global Snakebite Initiative and Médecins Sans Frontières [5,[16][17][18].The shortage of antivenoms can be in part counteracted by designing improved polyspecific antivenoms with a broad neutralizing spectrum, but also by a more rational use of existing antivenoms, i.e., through a systematic and detailed study of their paraspecificity. However, defining the venom cross-reactivity landscape of an antivenom is not a trivial matter, given the well-documented occurrence of venom variability in space (intra-and interpopulation) and time (ontogenetic) within and between all taxonomic levels [19][20][21][22]. This circumstance prevents the use of phylogenetic distance as a measure of venom compositional relatedness, even between closely-related species [23]. To assess the paraspecificity of antivenoms to the level of species-specific toxins, a proteomics-based protocol coined "antivenomics" was introduced in 2008, designed to quantify the extent of cross-reactivity of an antivenom against homologous and heterologous venoms at toxin resolution [24]. The initial protocol, which was based on the in-solution immunoprecipitation of antigen-antibody complexes followed by the chromatographic quantification of the free antigen present in the supenatant, was only suitable for whole IgG antivenoms. This "first generation" approach was subsequently re-designed for the assessment of F(ab') 2 and Fab antivenoms [25]. Key to this update was the immobilization of the antivenom molecules on a chromatographic matrix to generate an immunoaffinity column [25]. Among the most relevant advantages of this immunoaffinity-bas...

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“…Consequently, distinct antivenom products are produced (>45 manufacturers worldwide) to treat envenoming by numerous snake species found in different parts of the world, resulting in a highly fragmented drug market, issues with affordability, and a lack of sustainability 7,8 .…”

Section: Introductionmentioning

confidence: 99%

A therapeutic combination of two small molecule toxin inhibitors provides pancontinental preclinical efficacy against viper snakebite

Albulescu

Xie²,

Ainsworth³

et al. 2020

Preprint

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Snakebite is a medical emergency causing high mortality and morbidity in rural tropical communities that typically experience delayed access to unaffordable therapeutics. Viperid snakes are responsible for the majority of envenomings, but extensive interspecific variation in venom composition dictates that different antivenom treatments are used in different parts of the world, resulting in clinical and fiscal snakebite management challenges. Here, we show that a number of repurposed Phase 2-approved small molecules are capable of broadly neutralizing distinct viper venom bioactivities in vitro by inhibiting different enzymatic toxin families. Furthermore, using multiple in vivo models of envenoming, we demonstrate that a single dose of a rationally-selected dual inhibitor combination consisting of marimastat and varespladib prevents lethality caused by venom from the most medically-important vipers of Africa, South Asia and Central America. Our findings strongly support the translation of

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Vipers, mambas and taipans: the escalating health crisis over snakebites

Cited by 34 publications

References 5 publications

Haemotoxic snake venoms: their functional activity, impact on snakebite victims and pharmaceutical promise

Haemotoxic snake venoms: their functional activity, impact on snakebite victims and pharmaceutical promise

Third generation antivenomics: Pushing the limits of the in vitro preclinical assessment of antivenoms

A therapeutic combination of two small molecule toxin inhibitors provides pancontinental preclinical efficacy against viper snakebite

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