Coagulotoxicity of Bothrops (Lancehead Pit-Vipers) Venoms from Brazil: Differential Biochemistry and Antivenom Efficacy Resulting from Prey-Driven Venom Variation.

Leijiane Sousa,Francisco Coimbra,Kathleen Grego,Ana Moura Da Silva,Tiago Del-Rei,Amber Gillett,Sávio Sant’Anna,James Dobson,Christina Zdenek,Hipócrates Chalkidis,Marisa Teixeira-Da-Rocha,Bryan Fry,Bianca Op Den Brouw,Silvia Travaglia Cardoso

doi:10.3390/toxins10100411

Leijiane Sousa, Francisco Coimbra + Show 12 more

Open Access

https://doi.org/10.3390/toxins10100411

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Abstract

Lancehead pit-vipers (Bothrops genus) are an extremely diverse and medically important group responsible for the greatest number of snakebite envenomations and deaths in South America. Bothrops atrox (common lancehead), responsible for majority of snakebites and related deaths within the Brazilian Amazon, is a highly adaptable and widely distributed species, whose venom variability has been related to several factors, including geographical distribution and habitat type. This study examined venoms from four B. atrox populations (Belterra and Santarém, PA; Pres. Figueiredo, AM and São Bento, MA), and two additional Bothrops species (B. jararaca and B. neuwiedi) from Southeastern region for their coagulotoxic effects upon different plasmas (human, amphibian, and avian). The results revealed inter– and intraspecific variations in coagulotoxicity, including distinct activities between the three plasmas, with variations in the latter two linked to ecological niche occupied by the snakes. Also examined were the correlated biochemical mechanisms of venom action. Significant variation in the relative reliance upon the cofactors calcium and phospholipid were revealed, and the relative dependency did not significantly correlate with potency. Relative levels of Factor X or prothrombin activating toxins correlated with prey type and prey escape potential. The antivenom was shown to perform better in neutralising prothrombin activation activity than neutralising Factor X activation activity. Thus, the data reveal new information regarding the evolutionary selection pressures shaping snake venom evolution, while also having significant implications for the treatment of the envenomed patient. These results are, therefore, an intersection between evolutionary biology and clinical medicine.

Highlights

Snakebite is a global crisis due to its neglect relative to other tropical diseases [1]
In order to fill the aforementioned knowledge gaps, this study examined venoms of four populations of B. atrox snakes, captured from different habitat types within the Brazilian Amazon, in addition to two other Bothrops species, B. jararaca and B. neuwiedi, whose venoms are used for the production of the Instituto Butantan Bothrops antivenom
Significant variation was again evident in the procoagulant toxicity, with the Santarém population again considerably more toxic than the other B. atrox populations, in addition to

Summary

Introduction

Snakebite is a global crisis due to its neglect relative to other tropical diseases [1]. Of the coagulotoxin studies that have been undertaken, only some [3,4,5,6,7,8,9] have included in the experimental design the cofactors calcium and phospholipid, which are necessary to replicate physiological conditions in in vitro assays. Other studies have included only calcium [10,11,12,13,14,15], or neither cofactor [16,17,18], leading to deficiencies in replicating physiological conditions and interfering with accurate interpretation of the effects upon coagulation. The Bothrops genus (lancehead pit-vipers) is an extremely diverse [19] and medically significant snake group, responsible for the majority of envenomations and deaths related to snakebites in

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Conclusion