An analysis of venom ontogeny and prey-specific toxicity in the Monocled Cobra (Naja kaouthia)

Modahl, Cassandra M.; Mukherjee, Ashis K.; Mackessy, Stephen P.

doi:10.1016/j.toxicon.2016.04.049

Cited by 67 publications

(41 citation statements)

References 65 publications

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“…Calliotoxin lacks the second and third plesiotypic cysteines (Figure 2), similar to that of the classic Type I (aka: short-chain) α-neurotoxins, which also do not display a taxon specific effect [61,160]. This is consistent with the fact that while there are very few human C. bivirgatus envenomations on record, the majority were lethal.…”

Section: Resultssupporting

confidence: 66%

“…A problem that had also confounded studies of Boiga irregularis (brown tree snake), which had thus concluded they were non-venomous based on their effects in a murine model [150,151,152,153,154,155]. However, all such plesiotypic 3FTx rich venoms were later shown to be much more potent in a taxon-specific manner on diapsid (bird/reptile) than on synapsid (mammal) post-synaptic nicotinic acetylcholine receptors, with some non-front-fanged snakes being as potent as elapid snakes in such a taxon specific manner and thus were not ‘weak’ against natural prey items [59,82,130,156,157,158,159,160]. …”

Section: Resultsmentioning

confidence: 99%

“…It very well may be that while the α-neurotoxins are slower to take effect, they may be ultimately more effective as a consequence of their ability for sustained effect due to the pathology being produced due to simple steric inhibition. This is reflective in C. bivirgatus having a murine intravenous LD 50 of 0.7–0.8 mg/kg [81] in comparison to that of a venom almost exclusively containing classic α-neurotoxins such as Acanthophis antarcticus which has a murine intravenous LD 50 of 0.25 mg/kg [159,160]. Consistent with this, the black mamba ( Dendroaspis polylepis ), which consume a higher percentage of rodents than birds in their diet, has a murine intravenous LD 50 of 0.5 mg/kg, while the green mambas, which have a higher percentage of birds in their diets, and thus would benefit from less toxic but more rapidly acting knock-down venoms, have LD 50 s of over 2.5 mg/kg for the Eastern green mamba ( Dendroaspis angusticeps ), 0.9 mg/kg for the Jameson’s mamba ( Dendroaspis jamesoni ), and 1 mg/kg for the Western green mamba ( Dendroaspis viridis ) [161].…”

Section: Resultsmentioning

confidence: 99%

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The Snake with the Scorpion’s Sting: Novel Three-Finger Toxin Sodium Channel Activators from the Venom of the Long-Glanded Blue Coral Snake (Calliophis bivirgatus)

Yang

Deuis

Dashevsky

et al. 2016

Toxins

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Millions of years of evolution have fine-tuned the ability of venom peptides to rapidly incapacitate both prey and potential predators. Toxicofera reptiles are characterized by serous-secreting mandibular or maxillary glands with heightened levels of protein expression. These glands are the core anatomical components of the toxicoferan venom system, which exists in myriad points along an evolutionary continuum. Neofunctionalisation of toxins is facilitated by positive selection at functional hotspots on the ancestral protein and venom proteins have undergone dynamic diversification in helodermatid and varanid lizards as well as advanced snakes. A spectacular point on the venom system continuum is the long-glanded blue coral snake (Calliophis bivirgatus), a specialist feeder that preys on fast moving, venomous snakes which have both a high likelihood of prey escape but also represent significant danger to the predator itself. The maxillary venom glands of C. bivirgatus extend one quarter of the snake’s body length and nestle within the rib cavity. Despite the snake’s notoriety its venom has remained largely unstudied. Here we show that the venom uniquely produces spastic paralysis, in contrast to the flaccid paralysis typically produced by neurotoxic snake venoms. The toxin responsible, which we have called calliotoxin (δ-elapitoxin-Cb1a), is a three-finger toxin (3FTx). Calliotoxin shifts the voltage-dependence of NaV1.4 activation to more hyperpolarised potentials, inhibits inactivation, and produces large ramp currents, consistent with its profound effects on contractile force in an isolated skeletal muscle preparation. Voltage-gated sodium channels (NaV) are a particularly attractive pharmacological target as they are involved in almost all physiological processes including action potential generation and conduction. Accordingly, venom peptides that interfere with NaV function provide a key defensive and predatory advantage to a range of invertebrate venomous species including cone snails, scorpions, spiders, and anemones. Enhanced activation or delayed inactivation of sodium channels by toxins is associated with the extremely rapid onset of tetanic/excitatory paralysis in envenomed prey animals. A strong selection pressure exists for the evolution of such toxins where there is a high chance of prey escape. However, despite their prevalence in other venomous species, toxins causing delay of sodium channel inhibition have never previously been described in vertebrate venoms. Here we show that NaV modulators, convergent with those of invertebrates, have evolved in the venom of the long-glanded coral snake. Calliotoxin represents a functionally novel class of 3FTx and a structurally novel class of NaV toxins that will provide significant insights into the pharmacology and physiology of NaV. The toxin represents a remarkable case of functional convergence between invertebrate and vertebrate venom systems in response to similar selection pressures. These results underscore the dynamic evolution of the Toxicofera re...

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Section: Resultssupporting

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The Snake with the Scorpion’s Sting: Novel Three-Finger Toxin Sodium Channel Activators from the Venom of the Long-Glanded Blue Coral Snake (Calliophis bivirgatus)

Yang

Deuis

Dashevsky

et al. 2016

Toxins

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“…Both samples are finally analyzed by HPLC, and their profiles are compared to that of a control sample of venom. Quantitative estimations of the degree of immunorecognition of components are performed as described for panel b by integration of chromatographic peak areas [58]. d HPLC/ELISA-based assessment of immunorecognition of venom components by an antivenom, or HPLC/ELISA-based immunoprofiling, is performed by coating microwell plates with a normalized amount of venom fractions obtained from the HPLC profile of the venom.…”

Section: Antivenomics: the Immunorecognition Profiling Of Venom Antigensmentioning

confidence: 99%

Strategies in ‘snake venomics’ aiming at an integrative view of compositional, functional, and immunological characteristics of venoms

Lomonte

Calvete

2017

J Venom Anim Toxins Incl Trop Dis

129

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This work offers a general overview on the evolving strategies for the proteomic analysis of snake venoms, and discusses how these may be combined through diverse experimental approaches with the goal of achieving a more comprehensive knowledge on the compositional, toxic, and immunological characteristics of venoms. Some recent developments in this field are summarized, highlighting how strategies have evolved from the mere cataloguing of venom components (proteomics/venomics), to a broader exploration of their immunological (antivenomics) and functional (toxicovenomics) characteristics. Altogether, the combination of these complementary strategies is helping to build a wider, more integrative view of the life-threatening protein cocktails produced by venomous snakes, responsible for thousands of deaths every year.

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“…Thus, despite the fact that snake venoms are generally constituted by a limited number of protein families, there are variations in the proportion of each type of protein family in different venoms and, within a single protein family, there are many iso- and proteoforms with distinct toxicological and immunological profiles [16,17,18]. Elapid snake venoms are predominantly composed of neurotoxins or cytotoxins of the three-finger toxin family and phospholipases A 2 (PLA 2 ) [19,20,21]. Viperid venoms, in contrast, are composed mostly of PLA 2 s, zinc-dependent metalloproteinases (SVMPs) and serine proteinases (SVSPs) [22].…”

Section: Introductionmentioning

confidence: 99%

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

Gutiérrez

Solano

Plá

et al. 2017

Toxins

132

100

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Animal-derived antivenoms constitute the mainstay in the therapy of snakebite envenoming. The efficacy of antivenoms to neutralize toxicity of medically-relevant snake venoms has to be demonstrated through meticulous preclinical testing before their introduction into the clinical setting. The gold standard in the preclinical assessment and quality control of antivenoms is the neutralization of venom-induced lethality. In addition, depending on the pathophysiological profile of snake venoms, the neutralization of other toxic activities has to be evaluated, such as hemorrhagic, myotoxic, edema-forming, dermonecrotic, in vitro coagulant, and defibrinogenating effects. There is a need to develop laboratory assays to evaluate neutralization of other relevant venom activities. The concept of the 3Rs (Replacement, Reduction, and Refinement) in Toxinology is of utmost importance, and some advances have been performed in their implementation. A significant leap forward in the study of the immunological reactivity of antivenoms against venoms has been the development of “antivenomics”, which brings the analytical power of mass spectrometry to the evaluation of antivenoms. International partnerships are required to assess the preclinical efficacy of antivenoms against snake venoms in different regions of the world in order to have a detailed knowledge on the neutralizing profile of these immunotherapeutics.

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An analysis of venom ontogeny and prey-specific toxicity in the Monocled Cobra (Naja kaouthia)

Cited by 67 publications

References 65 publications

The Snake with the Scorpion’s Sting: Novel Three-Finger Toxin Sodium Channel Activators from the Venom of the Long-Glanded Blue Coral Snake (Calliophis bivirgatus)

The Snake with the Scorpion’s Sting: Novel Three-Finger Toxin Sodium Channel Activators from the Venom of the Long-Glanded Blue Coral Snake (Calliophis bivirgatus)

Strategies in ‘snake venomics’ aiming at an integrative view of compositional, functional, and immunological characteristics of venoms

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

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