Vipers of Major clinical relevance in Europe: Taxonomy, venom composition, toxicology and clinical management of human bites

Nicola, Matteo Riccardo Di; Pontara, Andrea; Kass, George E.N.; Kramer, Nynke I.; Avella, Ignazio; Pampena, Riccardo; Mercuri, Santo Raffaele; Dorne, Jean‐Lou; Paolino, Giovanni

doi:10.1016/j.tox.2021.152724

Cited by 53 publications

(51 citation statements)

References 95 publications

(120 reference statements)

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“…V. ammodytes meridionalis has been shown to share similar toxins as well as vipoxin (PLA 2 , postsynaptic neurotoxin) ( 74 ). The presence of additional toxin actions beyond those examined in this study is reflected in complex envenomation clinical profiles ( 61 ). Thus, more comprehensive in vitro assays and also in vivo studies must be conducted before clinical recommendations can be finalised regarding treatment options for particular species or populations within a species.…”

Section: Discussionmentioning

confidence: 90%

“…Another important caveat is that this study focused solely upon the coagulotoxic effects of these venoms. Each of these snake venoms has clinically relevant profile extending beyond coagulopathy, such as neurotoxicity, another major lethal trait ( 61 ). In addition to P-IIId SVMP, these venoms contain myriad other toxins, including snake venom serine protease (SVSP), phospholipase A 2 (PLA 2 ), and L-Amino acid oxidase (LAAO) ( 62 ).…”

Section: Discussionmentioning

confidence: 99%

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Venom-Induced Blood Disturbances by Palearctic Viperid Snakes, and Their Relative Neutralization by Antivenoms and Enzyme-Inhibitors

et al. 2021

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Palearctic vipers are medically significant snakes in the genera Daboia, Macrovipera, Montivipera, and Vipera which occur throughout Europe, Central Asia, Near and Middle East. While the ancestral condition is that of a small-bodied, lowland species, extensive diversification has occurred in body size, and niche specialization. Using 27 venom samples and a panel of in vitro coagulation assays, we evaluated the relative coagulotoxic potency of Palearctic viper venoms and compared their neutralization by three antivenoms (Insoserp Europe, VIPERFAV and ViperaTAb) and two metalloprotease inhibitors (prinomastat and DMPS). We show that variation in morphology parallels variation in the Factor X activating procoagulant toxicity, with the three convergent evolutions of larger body sizes (Daboia genus, Macrovipera genus, and Vipera ammodytes uniquely within the Vipera genus) were each accompanied by a significant increase in procoagulant potency. In contrast, the two convergent evolutions of high altitude specialization (the Montivipera genus and Vipera latastei uniquely within the Vipera genus) were each accompanied by a shift away from procoagulant action, with the Montivipera species being particularly potently anticoagulant. Inoserp Europe and VIPERFAV antivenoms were both effective against a broad range of Vipera species, with Inoserp able to neutralize additional species relative to VIPERFAV, reflective of its more complex antivenom immunization mixture. In contrast, ViperaTAb was extremely potent in neutralizing V. berus but, reflective of this being a monovalent antivenom, it was not effective against other Vipera species. The enzyme inhibitor prinomastat efficiently neutralized the metalloprotease-driven Factor X activation of the procoagulant venoms. In contrast, DMPS (2,3-dimercapto-1-propanesulfonic acid), which as been suggested as another potential treatment option in the absence of antivenom, DMPS failed against all venoms tested. Overall, our results highlight the evolutionary variations within Palearctic vipers and help to inform clinical management of viper envenomation.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Venom-Induced Blood Disturbances by Palearctic Viperid Snakes, and Their Relative Neutralization by Antivenoms and Enzyme-Inhibitors

et al. 2021

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“…Among the most dangerous true vipers, in terms of highest mortality, are the African Bitis arietans (puff adder) and Echis ocellatus (West African saw-scaled viper), as well as two of India’s ‘Big Four’, namely, Echis carinatus (Asian saw-scaled viper) and Daboia russelii (Russell’s viper) [ 12 , 15 ]. Nevertheless, viperid bites are also a critical health issue in the Middle East and even Europe [ 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…Some publications list several of those quantified venom proteomes, but Viperinae-related studies in particular constitute only a small part [ 61 , 62 , 63 ]. Although no up-to-date database summarizes all of these Viperinae studies in a comprehensive manner, there are a certain number of publications reviewing Viperinae venoms, that only focus on a few genera of high medical relevance or from exclusive areas [ 19 , 64 , 65 , 66 , 67 , 68 ]. However, there are many more studies on true vipers containing fully investigated venoms at the proteomic level.…”

Section: Introductionmentioning

confidence: 99%

Old World Vipers—A Review about Snake Venom Proteomics of Viperinae and Their Variations

Damm

Hempel

Süssmuth

2021

Toxins

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Fine-tuned by millions of years of evolution, snake venoms have frightened but also fascinated humanity and nowadays they constitute potential resources for drug development, therapeutics and antivenoms. The continuous progress of mass spectrometry techniques and latest advances in proteomics workflows enabled toxinologists to decipher venoms by modern omics technologies, so-called ‘venomics’. A tremendous upsurge reporting on snake venom proteomes could be observed. Within this review we focus on the highly venomous and widely distributed subfamily of Viperinae (Serpentes: Viperidae). A detailed public literature database search was performed (2003–2020) and we extensively reviewed all compositional venom studies of the so-called Old-World Vipers. In total, 54 studies resulted in 89 venom proteomes. The Viperinae venoms are dominated by four major, four secondary, six minor and several rare toxin families and peptides, respectively. The multitude of different venomics approaches complicates the comparison of venom composition datasets and therefore we differentiated between non-quantitative and three groups of quantitative workflows. The resulting direct comparisons within these groups show remarkable differences on the intra- and interspecies level across genera with a focus on regional differences. In summary, the present compilation is the first comprehensive up-to-date database on Viperinae venom proteomes and differentiating between analytical methods and workflows.

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“…Snakebite envenomation causes > 81,000 deaths and incapacities in another 400,000 people worldwide every year. Snake venoms are complex natural secretions comprised of hundreds of different molecules with a wide range of biological functions, which after injection cause local and systemic toxic manifestations (Di Nicola 2021 ; Acunha et al 2021 ).…”

mentioning

confidence: 99%

New aspects in snake venom toxicology

Bolt

2021

Arch Toxicol

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Vipers of Major clinical relevance in Europe: Taxonomy, venom composition, toxicology and clinical management of human bites

Cited by 53 publications

References 95 publications

Venom-Induced Blood Disturbances by Palearctic Viperid Snakes, and Their Relative Neutralization by Antivenoms and Enzyme-Inhibitors

Venom-Induced Blood Disturbances by Palearctic Viperid Snakes, and Their Relative Neutralization by Antivenoms and Enzyme-Inhibitors

Old World Vipers—A Review about Snake Venom Proteomics of Viperinae and Their Variations

New aspects in snake venom toxicology

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