Cloud serpent coagulotoxicity: The biochemical mechanisms underpinning the anticoagulant actions of Mixcoatlus and Ophryacus venoms

Youngman, Nicholas J.; Carlsson, Demi J.; Jones, Lee; Neri-Castro, Édgar; ́n, Alejandro Alago; Fry, Bryan G.

doi:10.1016/j.toxicon.2022.03.009

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…As the taxa that most potently inhibited FXa do not form a monophyletic clade (Figure 4), this suggests that FXa inhibition is a basal trait within this genus that has been amplified on three occasions and therefore an indication of convergence in adaptation. This is consistent with FXa inhibition having been documented in other pit vipers from the Americas, including the Bothriechis, Bothrops, Cerrophidion, Crotalus, and Ophryacus species [21,22,65,66]; Asian pit vipers, including the Deinagkistrodon and Gloydius species [65,67,68]; true vipers, including the Cerastes, Daboia, Pseudocerastes, and Vipera species [65,[69][70][71][72][73]; and elapid snakes including the Naja and Pseudechis species [14,41,74,75]. The toxin types responsible are diverse, including Kunitz peptides, lectin-framework toxins, and phospholipases A 2 .…”

Section: Resultssupporting

confidence: 89%

“…A myriad of toxin types have been isolated and characterised from snake venoms that disrupt blood coagulation, with the venoms of viperid snakes being particularly rich in such toxins. The effects of anticoagulant toxins include the inhibition of the clotting enzymes thrombin, VIIa, Xa, IXa, XIa, and XIIa and the depletion of fibrinogen levels, leading to death from haemorrhagic shock or internal bleeding [13][14][15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Blood Lines: Intraspecific and Interspecific Variations in Anticoagulant Actions of Agkistrodon Viperid Venoms

Coimbra,

Sanchez,

Lomonte

et al. 2024

Toxins

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This study investigated the intraspecific and interspecific variability in the venom effects of Agkistrodon viperid snake species and subspecies (eleven venoms total) on plasma clotting times, fibrinogen levels, and fibrin clot strength. Significant delays in plasma clotting time were observed for A. conanti, A. contortrix mokasen, A. contortrix phaeogaster, A. howardgloydi, A. piscivorus leucostoma, and A. piscivorus piscivorus. Notably, the phylogenetically disjunct lineages A. conanti, A. contortrix mokasen, and A. howardgloydi exhibited the most potent anticoagulant effects, indicating the independent amplification of a basal trait. Inhibition assays with the activated clotting enzymes Factors XIa, IXa, Xa, and IIa (thrombin) revealed that FXa inhibition is another basal trait amplified independently on multiple occasions within the genus, but with A. howardgloydi, notably more potent than all others. Phospholipid degradation and zymogen destruction were identified as mechanisms underlying the variability in venom effects observed experimentally and in previous clinical reports. Thromboelastography demonstrated that the venoms did not clot fibrinogen directly but affected fibrin clot strength by damaging fibrinogen and that thrombin was subsequently only able to cleave into weak, unstable clots. The ability to activate Protein C, an endogenous anticoagulant enzyme, varied across species, with some venoms exceeding that of A. contortrix contortrix, which previously yielded the protein diagnostic agent Protac®. Phylogenetic analysis suggested that both fibrinogen degradation and Protein C activation were each amplified multiple times within the genus, albeit with negative correlation between these two modes of action. This study highlights the evolutionary, clinical, and biodiscovery implications of venom variability in the Agkistrodon species, underscoring their dynamic evolution, emphasising the need for tailored clinical approaches, and highlighting the potential for novel diagnostic and therapeutic developments inspired by the unique properties of snake venoms.

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Section: Resultssupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Blood Lines: Intraspecific and Interspecific Variations in Anticoagulant Actions of Agkistrodon Viperid Venoms

Coimbra,

Sanchez,

Lomonte

et al. 2024

Toxins

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“…The most basal species, B. pictus [ 71 , 80 ], was like most non- Bothrops American pit vipers [ 37 , 55 , 56 , 81 ] in that it lacked procoagulant venom; it was anticoagulant on human plasma ( Figure 1 and Figure 2 ). This result might be indicative of the common ancestor of all Bothrops having a distinct anticoagulant venom action compared to the often procoagulant action seen in the more derived Bothrops .…”

Section: Discussionmentioning

confidence: 99%

Clinical and Evolutionary Implications of Dynamic Coagulotoxicity Divergences in Bothrops (Lancehead Pit Viper) Venoms

Bourke

Zdenek

Tanaka-Azevedo

et al. 2022

Toxins

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Despite coagulotoxicity being a primary weapon for prey capture by Bothrops species (lancehead pit vipers) and coagulopathy being a major lethal clinical effect, a genus-wide comparison has not been undertaken. To fill this knowledge gap, we used thromboelastography to compare 37 venoms, from across the full range of geography, taxonomy, and ecology, for their action upon whole plasma and isolated fibrinogen. Potent procoagulant toxicity was shown to be the main venom effect of most of the species tested. However, the most basal species (B. pictus) was strongly anticoagulant; this is consistent with procoagulant toxicity being a novel trait that evolved within Bothrops subsequent to their split from anticoagulant American pit vipers. Intriguingly, two of the arboreal species studied (B. bilineatus and B. taeniatus) lacked procoagulant venom, suggesting differential evolutionary selection pressures. Notably, some terrestrial species have secondarily lost the procoagulant venom trait: the Mogi Mirim, Brazil locality of B. alternatus; San Andres, Mexico locality of B. asper; B. diporus; and the São Roque of B. jararaca. Direct action on fibrinogen was extremely variable; this is consistent with previous hypotheses regarding it being evolutionary decoupled due to procoagulant toxicity being the primary prey-capture weapon. However, human patients live long enough for fibrinogen depletion to be clinically significant. The extreme variability may be reflective of antivenom variability, with these results thereby providing a foundation for such future work of clinical relevance. Similarly, the venom diversification trends relative to ecological niche will also be useful for integration with natural history data, to reconstruct the evolutionary pressures shaping the venoms of these fascinating snakes.

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Transient Hematotoxicity After Emerald Horned Pitviper (Ophryacus smaragdinus) Envenomation: A Case Report

Shumway,

Pho,

Andrews

et al. 2024

The Journal of Emergency Medicine

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Cloud serpent coagulotoxicity: The biochemical mechanisms underpinning the anticoagulant actions of Mixcoatlus and Ophryacus venoms

Cited by 3 publications

References 26 publications

Blood Lines: Intraspecific and Interspecific Variations in Anticoagulant Actions of Agkistrodon Viperid Venoms

Blood Lines: Intraspecific and Interspecific Variations in Anticoagulant Actions of Agkistrodon Viperid Venoms

Clinical and Evolutionary Implications of Dynamic Coagulotoxicity Divergences in Bothrops (Lancehead Pit Viper) Venoms

Transient Hematotoxicity After Emerald Horned Pitviper (Ophryacus smaragdinus) Envenomation: A Case Report

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