Widespread and Differential Neurotoxicity in Venoms from the Bitis Genus of Viperid Snakes

Youngman, Nicholas J.; Harris, Richard J.; Huynh, Tam Minh; Coster, Kristian; Sundman, Eric; Braun, Ralph; Naude, Arno; Hodgson, Wayne C.; Fry, Bryan G.

doi:10.1007/s12640-021-00330-4

Cited by 12 publications

(15 citation statements)

References 47 publications

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“…The other major group of snake neurotoxins are the post-synaptically acting α-neurotoxins. These toxins are present in venoms from a range of snakes, including many species that do not result in paralysis in humans (Barber et al, 2013;Youngman et al, 2021). The proportion of α-neurotoxins in snake venoms is known to be associated with the prey selectivity of the venoms (Harris et al, 2020), which further suggests that these particular toxins are animal-specific.…”

Section: Introductionmentioning

confidence: 99%

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Rodent Lethality Models Are Problematic for Evaluating Antivenoms for Human Envenoming

et al. 2022

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Section: Introductionmentioning

confidence: 99%

“…(Gutiérrez et al, 1988;Bard et al, 1994;Diniz-Sousa et al, 2020). Although α-neurotoxins are mostly found in elapids and colubrids, they are present even in some viperid venoms that do not cause neurotoxicity in humans, such as Puff adders (Wang et al, 2020;Youngman et al, 2021) hence the utility of these assays remains narrow.…”

Section: Introductionmentioning

confidence: 99%

Rodent Lethality Models Are Problematic for Evaluating Antivenoms for Human Envenoming

et al. 2022

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“…This BLI method has successfully revealed taxon-selective neurotoxicity such as preferential binding to a snake target by the snake-feeding specialist Ophiophagus hannah (King Cobra), fish by sea snakes, and amphibians for cobras (Harris et al 2020c ; Zdenek et al 2019 ). This method has also facilitated the characterization of neurotoxicity in species not previously tested for these effects, including the Asian pit viper species Calloselasma rhodostoma , species within the African viperid genus Bitis , and the Central American arboreal genus Bothriechis (Harris et al 2020b ; Youngman et al 2021 , 2022 ). Further garnered from the BLI method are the residues responsible for venom resistance that convergently evolved in diverse animals ranging from the Honey Badger ( Mellivora capensis ) to the Burmese Python ( Python bivittatus ) to the Savannah Monitor Lizard ( Varanus exanthematicus ) to primates (Harris and Fry 2021 ; Harris et al 2021 ; Jones et al 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Diverse and Dynamic Alpha-Neurotoxicity Within Venoms from the Palearctic Viperid Snake Clade of Daboia, Macrovipera, Montivipera, and Vipera

2022

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The targeting of specific prey by snake venom toxins is a fascinating aspect of molecular and ecological evolution. Neurotoxic targeting by elapid snakes dominates the literature in this regard; however, recent studies have revealed viper toxins also induce neurotoxic effect. While this effect is thought to primarily be driven by prey selectivity, no study has quantified the taxonomically specific neurotoxicity of the viper clade consisting of Daboia, Macrovipera, Montivipera, and Vipera genera. Here, we tested venom toxin binding from 28 species of vipers from the four genera on the alpha 1 neuronal nicotinic acetylcholine receptors (nAChRs) orthosteric sites of amphibian, avian, lizard, rodent, and human mimotopes (synthetic peptides) using the Octet HTX biolayer interferometry platform. Daboia siamensis and D. russelii had broad binding affinity towards all mimotopes, while D. palestinae had selectivity toward lizard. Macrovipera species, on the other hand, were observed to have a higher affinity for amphibian mimotopes except for M. schweizeri, which inclined more toward lizard mimotopes. All Montivipera and most Vipera species also had higher affinity toward lizard mimotopes. Vipera a. montandoni, V. latastei, V. nikolski, and V. transcaucasina had the least binding to any of the mimotopes of the study. While a wide range of affinity binding towards various mimotopes were observed within the clade, the lowest affinity occurred towards the human target. Daboia siamensis and Macrovipera lebetina exhibited the greatest affinity toward the human mimotope, albeit still the least targeted of the mimotopes within those species. Overlaying this toxin-targeting trait over phylogeny of this clade revealed multiple cases of amplification of this trait and several cases of secondary loss. Overall, our results reveal dynamic variation, amplification, and some secondary loss of the prey targeting trait by alpha-neurotoxins within the venoms of this clade, indicating evolutionary selection pressure shaping the basic biochemistry of these venoms. Our work illustrates the successful use of this biophysical assay to further research snake venom neurotoxins and emphasizes the risk of generalizing venom effects observed on laboratory animals to have similar effects on humans.

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“…The venom was tested in triplicate (n = 3). The control was venom from Crotalus horridus which has been used previously as a control for nAChR binding (Harris et al, 2020a, b;Youngman et al, 2021) since there is no nAChR binding toxins within the venom. Error bars on all graphs represent the SEM (error bars on graph B are represented by dots surrounding the curves).…”

Section: Introductionmentioning

confidence: 99%

Getting stoned: Characterisation of the coagulotoxic and neurotoxic effects of reef stonefish (Synanceia verrucosa) venom

et al. 2021

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Widespread and Differential Neurotoxicity in Venoms from the Bitis Genus of Viperid Snakes

Cited by 12 publications

References 47 publications

Rodent Lethality Models Are Problematic for Evaluating Antivenoms for Human Envenoming

Rodent Lethality Models Are Problematic for Evaluating Antivenoms for Human Envenoming

Diverse and Dynamic Alpha-Neurotoxicity Within Venoms from the Palearctic Viperid Snake Clade of Daboia, Macrovipera, Montivipera, and Vipera

Getting stoned: Characterisation of the coagulotoxic and neurotoxic effects of reef stonefish (Synanceia verrucosa) venom

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