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Juan J. Calvete
Evolutionary and Translational Venomics Laboratory, Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain

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Journal article
Published: 12 June 2021 in Toxicon: X
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Snakebite envenoming is a neglected tropical disease that may claim over 100,000 human lives annually worldwide. Snakebite occurs as the result of an interaction between a human and a snake that elicits either a defensive response from the snake or, more rarely, a feeding response as the result of mistaken identity. Snakebite envenoming is therefore a biological and, more specifically, an ecological problem. Snake venom itself is often described as a “cocktail”, as it is a heterogenous mixture of molecules including the toxins (which are typically proteinaceous) responsible for the pathophysiological consequences of envenoming. The primary function of venom in snake ecology is pre-subjugation, with defensive deployment of the secretion typically considered a secondary function. The particular composition of any given venom cocktail is shaped by evolutionary forces that include phylogenetic constraints associated with the snake's lineage and adaptive responses to the snake's ecological context, including the taxa it preys upon and by which it is predated upon. In the present article, we describe how conceptual frameworks from ecology and evolutionary biology can enter into a mutually enlightening relationship with clinical toxinology by enabling the consideration of snakebite envenoming from an “ecological stance”. We detail the insights that may emerge from such a perspective and highlight the ways in which the high-fidelity descriptive knowledge emerging from applications of -omics era technologies – “venomics” and “antivenomics” – can combine with evolutionary explanations to deliver a detailed understanding of this multifactorial health crisis.

ACS Style

Juan J. Calvete; Bruno Lomonte; Anthony J. Saviola; Fabián Bonilla; Mahmood Sasa; David J. Williams; Eivind A.B. Undheim; Kartik Sunagar; Timothy N.W. Jackson. Mutual enlightenment: A toolbox of concepts and methods for integrating evolutionary and clinical toxinology via snake venomics and the contextual stance. Toxicon: X 2021, 9-10, 100070 .

AMA Style

Juan J. Calvete, Bruno Lomonte, Anthony J. Saviola, Fabián Bonilla, Mahmood Sasa, David J. Williams, Eivind A.B. Undheim, Kartik Sunagar, Timothy N.W. Jackson. Mutual enlightenment: A toolbox of concepts and methods for integrating evolutionary and clinical toxinology via snake venomics and the contextual stance. Toxicon: X. 2021; 9-10 ():100070.

Chicago/Turabian Style

Juan J. Calvete; Bruno Lomonte; Anthony J. Saviola; Fabián Bonilla; Mahmood Sasa; David J. Williams; Eivind A.B. Undheim; Kartik Sunagar; Timothy N.W. Jackson. 2021. "Mutual enlightenment: A toolbox of concepts and methods for integrating evolutionary and clinical toxinology via snake venomics and the contextual stance." Toxicon: X 9-10, no. : 100070.

Review article
Published: 30 April 2021 in Biochemical Society Transactions
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This short essay pretends to make the reader reflect on the concept of biological mass and on the added value that the determination of this molecular property of a protein brings to the interpretation of evolutionary and translational snake venomics research. Starting from the premise that the amino acid sequence is the most distinctive primary molecular characteristics of any protein, the thesis underlying the first part of this essay is that the isotopic distribution of a protein's molecular mass serves to unambiguously differentiate it from any other of an organism's proteome. In the second part of the essay, we discuss examples of collaborative projects among our laboratories, where mass profiling of snake venom PLA2 across conspecific populations played a key role revealing dispersal routes that determined the current phylogeographic pattern of the species.

ACS Style

Juan J. Calvete; Libia Sanz; Diana Mora-Obando; Bruno Lomonte; Anita M. Tanaka-Azevedo; Karen de Morais-Zani; Sávio S. Sant'Anna; Cleópatra A.S. Caldeira. What's in a mass? Biochemical Society Transactions 2021, 49, 1027 -1037.

AMA Style

Juan J. Calvete, Libia Sanz, Diana Mora-Obando, Bruno Lomonte, Anita M. Tanaka-Azevedo, Karen de Morais-Zani, Sávio S. Sant'Anna, Cleópatra A.S. Caldeira. What's in a mass? Biochemical Society Transactions. 2021; 49 (2):1027-1037.

Chicago/Turabian Style

Juan J. Calvete; Libia Sanz; Diana Mora-Obando; Bruno Lomonte; Anita M. Tanaka-Azevedo; Karen de Morais-Zani; Sávio S. Sant'Anna; Cleópatra A.S. Caldeira. 2021. "What's in a mass?" Biochemical Society Transactions 49, no. 2: 1027-1037.

Review
Published: 22 April 2021 in International Journal of Molecular Sciences
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Seminal plasma (SP), the non-cellular component of semen, is a heterogeneous composite fluid built by secretions of the testis, the epididymis and the accessory sexual glands. Its composition, despite species-specific anatomical peculiarities, consistently contains inorganic ions, specific hormones, proteins and peptides, including cytokines and enzymes, cholesterol, DNA and RNA—the latter often protected within epididymis- or prostate-derived extracellular vesicles. It is beyond question that the SP participates in diverse aspects of sperm function pre-fertilization events. The SP also interacts with the various compartments of the tubular genital tract, triggering changes in gene function that prepares for an eventual successful pregnancy; thus, it ultimately modulates fertility. Despite these concepts, it is imperative to remember that SP-free spermatozoa (epididymal or washed ejaculated) are still fertile, so this review shall focus on the differences between the in vivo roles of the SP following semen deposition in the female and those regarding additions of SP on spermatozoa handled for artificial reproduction, including cryopreservation, from artificial insemination to in vitro fertilization. This review attempts, including our own results on model animal species, to critically summarize the current knowledge of the reproductive roles played by SP components, particularly in our own species, which is increasingly affected by infertility. The ultimate goal is to reconcile the delicate balance between the SP molecular concentration and their concerted effects after temporal exposure in vivo. We aim to appraise the functions of the SP components, their relevance as diagnostic biomarkers and their value as eventual additives to refine reproductive strategies, including biotechnologies, in livestock models and humans.

ACS Style

Heriberto Rodriguez-Martinez; Emilio Martinez; Juan Calvete; Fernando Peña Vega; Jordi Roca. Seminal Plasma: Relevant for Fertility? International Journal of Molecular Sciences 2021, 22, 4368 .

AMA Style

Heriberto Rodriguez-Martinez, Emilio Martinez, Juan Calvete, Fernando Peña Vega, Jordi Roca. Seminal Plasma: Relevant for Fertility? International Journal of Molecular Sciences. 2021; 22 (9):4368.

Chicago/Turabian Style

Heriberto Rodriguez-Martinez; Emilio Martinez; Juan Calvete; Fernando Peña Vega; Jordi Roca. 2021. "Seminal Plasma: Relevant for Fertility?" International Journal of Molecular Sciences 22, no. 9: 4368.

Journal article
Published: 26 March 2021 in Journal of Proteomics
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Cobras are the most medically important elapid snakes in Africa. The African genera Naja and Hemachatus include snakes with neurotoxic and cytotoxic venoms, with shared biochemical, toxinological and antigenic characteristics. We have studied the antigenic cross-reactivity of four sub-Saharan Africa cobra venoms against an experimental monospecific Hemachatus haemachatus antivenom through comparative proteomics, preclinical assessment of neutralization, and third generation antivenomics. The venoms of H. haemachatus, N. annulifera, N. mossambica and N. nigricollis share an overall qualitative family toxin composition but depart in their proportions of three-finger toxin (3FTxs) classes, phospholipases A2 (PLA2s), snake venom metalloproteinases (SVMPs), and cysteine-rich secretory proteins (CRISPs). A monospecific anti-Hemachatus antivenom produced by Costa Rican Instituto Clodomiro Picado neutralized the lethal activity of the homologous and heterologous neuro/cytotoxic (H. haemachatus) and cyto/cardiotoxic (N. mossambica and N. nigricollis) venoms of the three spitting cobras sampled, while it was ineffective against the lethal and toxic activities of the neurotoxic venom of the non-spitting snouted cobra N. annulifera. The ability of the anti-Hemachatus-ICP antivenom to neutralize toxic (dermonecrotic and anticoagulant) and enzymatic (PLA2) activities of spitting cobra venoms suggested a closer kinship of H. haemachatus and Naja subgenus Afrocobra spitting cobras than to Naja subgenus Uraeus neurotoxic taxa. These results were confirmed by third generation antivenomics. African Naja species represent the most widespread medically important elapid snakes across Africa. To gain deeper insight into the spectrum of medically relevant toxins, we compared the proteome of three spitting cobras (Hemachatus haemachatus, Naja mossambica and N. nigricollis) and one non-spitting cobra (N. annulifera). Three finger toxins and phospholipases A2 are the two major protein families among the venoms analyzed. The development of antivenoms of broad species coverage is an urgent need in sub-Saharan Africa. An equine antivenom raised against H. haemachatus venom showed cross-reactivity with the venoms of H. haemachatus, N. mossambica and N. nigricollis, while having poor recognition of the venom of N. annulifera. This immunological information provides clues for the design of optimum venom mixtures for the preparation of broad spectrum antivenoms.

ACS Style

Andrés Sánchez; Álvaro Segura; Davinia Pla; José Munuera; Mauren Villalta; Sarai Quesada-Bernat; Daniel Chavarría; María Herrera; José María Gutiérrez; Guillermo León; Juan J. Calvete; Mariángela Vargas. Comparative venomics and preclinical efficacy evaluation of a monospecific Hemachatus antivenom towards sub-Saharan Africa cobra venoms. Journal of Proteomics 2021, 240, 104196 .

AMA Style

Andrés Sánchez, Álvaro Segura, Davinia Pla, José Munuera, Mauren Villalta, Sarai Quesada-Bernat, Daniel Chavarría, María Herrera, José María Gutiérrez, Guillermo León, Juan J. Calvete, Mariángela Vargas. Comparative venomics and preclinical efficacy evaluation of a monospecific Hemachatus antivenom towards sub-Saharan Africa cobra venoms. Journal of Proteomics. 2021; 240 ():104196.

Chicago/Turabian Style

Andrés Sánchez; Álvaro Segura; Davinia Pla; José Munuera; Mauren Villalta; Sarai Quesada-Bernat; Daniel Chavarría; María Herrera; José María Gutiérrez; Guillermo León; Juan J. Calvete; Mariángela Vargas. 2021. "Comparative venomics and preclinical efficacy evaluation of a monospecific Hemachatus antivenom towards sub-Saharan Africa cobra venoms." Journal of Proteomics 240, no. : 104196.

Research article
Published: 01 February 2021 in PLOS Neglected Tropical Diseases
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Background Bothrops asper represents the clinically most important snake species in Central America and Northern South America, where it is responsible for an estimated 50–80% of snakebites. Compositional variability among the venom proteomes of B. asper lineages across its wide range mirrors clinical differences in their envenomings. Bothropic antivenoms generated in a number of Latin American countries commonly exhibit a certain degree of paraspecific effectiveness in the neutralization of congeneric venoms. Defining the phylogeographic boundaries of an antivenom's effectivity has implications for optimizing its clinical use. However, the molecular bases and impact of venom compositions on the immune recognition and neutralization of the toxic activities of across geographically disparate populations of B. asper lineages has not been comprehensively studied. Methodology/Principal findings Third-generation antivenomics was applied to quantify the cross-immunorecognizing capacity against the individual components of venoms of three B. asper lineages (B. asper (sensu stricto), B. ayerbei and B. rhombeatus) distributed in south-western (SW) Colombia, of six Latin American antivenoms, produced against homologous (Colombia, INS-COL and PROBIOL) and Costa Rica (ICP)), and heterologous (Argentina (BIOL), Perú (INS-PERU) and Venezuela (UCV)) bothropic venoms. In vivo neutralization assays of the lethal, hemorrhagic, coagulant, defibrinogenating, myotoxic, edematogenic, indirect hemolytic, and proteolytic activities of the three SW Colombian B. asper lineage venoms were carried to compare the preclinical efficacy of three (Colombian INS-COL and PROBIOL, and Costa Rican ICP) antivenoms frequently used in Colombia. Antivenomics showed that all the six antivenom affinity matrices efficiently immunoretained most of the B. asper lineages venom proteins and exhibited impaired binding towards the venoms' peptidomes. The neutralization profile of the INS-COL, PROBIOL and ICP antivenoms towards the biological activities of the venoms of SW Colombian B. asper (sensu stricto), B. ayerbei and B. rhombeatus lineages was coherent with the antivenomics outcome. In addition, the combination of in vitro (antivenomics) and in vivo neutralization results allowed us to determine their toxin-specific and venom neutralizing antibody content. Noteworthy, heterologous INS-PERU, BIOL, and UCV bothropic antivenoms had equal or higher binding capacity towards the venoms components of SW Colombian B. asper lineages that the homologous Colombian and Costa Rican antivenoms. Conclusions/Significance The combined in vitro and in vivo preclinical outcome showed that antivenoms manufactured in Colombia and Costa Rica effectively neutralize the major toxic activities of SW Colombian B. asper lineage venoms. The antivenomics profiles of the heterologous antivenoms manufactured in Argentina, Venezuela, and Perú strongly suggests their (pre)clinical adequacy for the treatment of B. asper lineage envenomings in SW Colombia. However, their recommendation in the clinical setting is pending on in vivo neutralization testing and clinical testing in humans. Bothrops asper is a highly adaptable snake species complex, which is considered the most dangerous snake throughout much of its distribution range from the Atlantic lowland of eastern México to northwestern Perú. Antivenoms are the only scientifically validated treatment of snakebite envenomings. Venom variation is particularly common in wide ranging species, such as B. asper, and may result in variable clinical presentations of envenomings, as is the case for the B. asper species complex, potentially undermining the efficacy of snakebite treatments depending on the immunization mixture used in the generation of the antivenom. Conversely, phylogenetic conservation of antigenic determinants confers an unpredictable degree of paraspecificity to homologous antivenoms produced for a geographic area, but also to heterologous congeneric antivenoms, towards the venom components of allopatric conspecific populations. This work aimed at comparing the preclinical profile of a panel of Latin American homologous and heterologous antivenoms against the venoms of B. asper lineages distributed in SW Colombia. The outcome of this study strongly suggests the suitability of considering the heterologous antivenoms BIOL (Argentina), UCV (Venezuela) and INS-PERU (Perú) as alternatives to homologous Colombian INS-COL and PROBIOL and Costa Rican ICP antivenoms for the treatment of envenomings by B. asper (sensu stricto) in W Colombia and Ecuador, B. ayerbei in Cauca and Nariño (Colombia), and B. rhombeatus in Cauca river valley, SW Colombia.

ACS Style

Diana Mora-Obando; Davinia Pla; Bruno Lomonte; Jimmy Alexander Guerrero-Vargas; Santiago Ayerbe; Juan J. Calvete. Antivenomics and in vivo preclinical efficacy of six Latin American antivenoms towards south-western Colombian Bothrops asper lineage venoms. PLOS Neglected Tropical Diseases 2021, 15, e0009073 .

AMA Style

Diana Mora-Obando, Davinia Pla, Bruno Lomonte, Jimmy Alexander Guerrero-Vargas, Santiago Ayerbe, Juan J. Calvete. Antivenomics and in vivo preclinical efficacy of six Latin American antivenoms towards south-western Colombian Bothrops asper lineage venoms. PLOS Neglected Tropical Diseases. 2021; 15 (2):e0009073.

Chicago/Turabian Style

Diana Mora-Obando; Davinia Pla; Bruno Lomonte; Jimmy Alexander Guerrero-Vargas; Santiago Ayerbe; Juan J. Calvete. 2021. "Antivenomics and in vivo preclinical efficacy of six Latin American antivenoms towards south-western Colombian Bothrops asper lineage venoms." PLOS Neglected Tropical Diseases 15, no. 2: e0009073.

Report
Published: 21 January 2021 in Science
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Convergent evolution provides insights into the selective drivers underlying evolutionary change. Snake venoms, with a direct genetic basis and clearly defined functional phenotype, provide a model system for exploring the repeated evolution of adaptations. While snakes use venom primarily for predation, and venom composition often reflects diet specificity, three lineages of cobras have independently evolved the ability to spit venom at adversaries. Using gene, protein, and functional analyses, we show that the three spitting lineages possess venoms characterized by an up-regulation of phospholipase A2 (PLA2) toxins, which potentiate the action of preexisting venom cytotoxins to activate mammalian sensory neurons and cause enhanced pain. These repeated independent changes provide a fascinating example of convergent evolution across multiple phenotypic levels driven by selection for defense.

ACS Style

T. D. Kazandjian; D. Petras; S. D. Robinson; J. van Thiel; H. W. Greene; K. Arbuckle; A. Barlow; D. A. Carter; R. M. Wouters; G. Whiteley; S. C. Wagstaff; A. S. Arias; L.-O. Albulescu; A. Plettenberg Laing; C. Hall; A. Heap; S. Penrhyn-Lowe; C. V. McCabe; S. Ainsworth; R. R. da Silva; P. C. Dorrestein; M. K. Richardson; J. M. Gutiérrez; J. J. Calvete; R. A. Harrison; I. Vetter; E. A. B. Undheim; W. Wüster; N. R. Casewell. Convergent evolution of pain-inducing defensive venom components in spitting cobras. Science 2021, 371, 386 -390.

AMA Style

T. D. Kazandjian, D. Petras, S. D. Robinson, J. van Thiel, H. W. Greene, K. Arbuckle, A. Barlow, D. A. Carter, R. M. Wouters, G. Whiteley, S. C. Wagstaff, A. S. Arias, L.-O. Albulescu, A. Plettenberg Laing, C. Hall, A. Heap, S. Penrhyn-Lowe, C. V. McCabe, S. Ainsworth, R. R. da Silva, P. C. Dorrestein, M. K. Richardson, J. M. Gutiérrez, J. J. Calvete, R. A. Harrison, I. Vetter, E. A. B. Undheim, W. Wüster, N. R. Casewell. Convergent evolution of pain-inducing defensive venom components in spitting cobras. Science. 2021; 371 (6527):386-390.

Chicago/Turabian Style

T. D. Kazandjian; D. Petras; S. D. Robinson; J. van Thiel; H. W. Greene; K. Arbuckle; A. Barlow; D. A. Carter; R. M. Wouters; G. Whiteley; S. C. Wagstaff; A. S. Arias; L.-O. Albulescu; A. Plettenberg Laing; C. Hall; A. Heap; S. Penrhyn-Lowe; C. V. McCabe; S. Ainsworth; R. R. da Silva; P. C. Dorrestein; M. K. Richardson; J. M. Gutiérrez; J. J. Calvete; R. A. Harrison; I. Vetter; E. A. B. Undheim; W. Wüster; N. R. Casewell. 2021. "Convergent evolution of pain-inducing defensive venom components in spitting cobras." Science 371, no. 6527: 386-390.

Journal article
Published: 25 November 2020 in Toxicon
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Based on its mandibular gland secretion, the earless monitor lizard, Lanthanotus borneensis, has been considered a venomous animal like other members of the Toxicofera group, including Heloderma. In the present study, the gland structure and teeth of L. borneensis were examined by micro-tomography (μCT) and scanning electron microscopy (SEM), respectively, and proteomic analysis of the gland extract was performed. The mandibular gland consists of six compartments with separate ducts. The pleurodont teeth of the lower and upper jaw are not grooved but possess a sharp ridge on the anterior surface. Proteomic analysis of the gland extract confirmed previous studies that kallikrein enzymes are the major biologically active components. In view of the lizard's biology, its mandibular gland secretion is obviously not needed for prey capture or defence. It seems not justified the labelling of L. borneensis as a venomous animal. However, definitively answering this question requires toxinological studies on natural prey.

ACS Style

Dietrich Mebs; Bruno Lomonte; Julián Fernández; Juan J. Calvete; Libia Sanz; Kristin Mahlow; Johannes Müller; Gunther Köhler; Michael Zollweg. The earless monitor lizard Lanthanotus borneensis – A venomous animal? Toxicon 2020, 189, 73 -78.

AMA Style

Dietrich Mebs, Bruno Lomonte, Julián Fernández, Juan J. Calvete, Libia Sanz, Kristin Mahlow, Johannes Müller, Gunther Köhler, Michael Zollweg. The earless monitor lizard Lanthanotus borneensis – A venomous animal? Toxicon. 2020; 189 ():73-78.

Chicago/Turabian Style

Dietrich Mebs; Bruno Lomonte; Julián Fernández; Juan J. Calvete; Libia Sanz; Kristin Mahlow; Johannes Müller; Gunther Köhler; Michael Zollweg. 2020. "The earless monitor lizard Lanthanotus borneensis – A venomous animal?" Toxicon 189, no. : 73-78.

Conference paper
Published: 12 October 2020 in Bioscientifica Proceedings
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ACS Style

Heriberto Rodriguez-Martinez; U. Kvist; F. Saravia; M. Wallgren; A. Johannissono; Libia Sanz; Fernando J Peña; Emilio A Martinez; J. Roca; Juan Maria Vazquez; Juan Calvete. The physiological roles of the boar ejaculate. Bioscientifica Proceedings 2020, 1 .

AMA Style

Heriberto Rodriguez-Martinez, U. Kvist, F. Saravia, M. Wallgren, A. Johannissono, Libia Sanz, Fernando J Peña, Emilio A Martinez, J. Roca, Juan Maria Vazquez, Juan Calvete. The physiological roles of the boar ejaculate. Bioscientifica Proceedings. 2020; ():1.

Chicago/Turabian Style

Heriberto Rodriguez-Martinez; U. Kvist; F. Saravia; M. Wallgren; A. Johannissono; Libia Sanz; Fernando J Peña; Emilio A Martinez; J. Roca; Juan Maria Vazquez; Juan Calvete. 2020. "The physiological roles of the boar ejaculate." Bioscientifica Proceedings , no. : 1.

Journal article
Published: 20 August 2020 in Journal of Proteomics
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Bothrops asper is a venomous pitviper that is widely distributed and of clinical importance in Mesoamerica and northern South America, where it is responsible for 50–80% of all envenomations by Viperidae species. Previous work suggests that B. asper has a complex phylogeographic structure, with the existence of multiple evolutionarily distinct lineages, particularly in the inter-Andean valleys of north South America. To explore the impact of the evolutionary history of B. asper on venom composition, we have investigated geographic variation in the venom proteome of this species from the populations from the Pacific side of Ecuador and south-western Colombia. Among the 21 classes of venom components identified, proteins from mainly four major toxin families, snake venom metalloproteases (PI- and PII-SVMP), phospholipases A2 (K49- and D49-PLA2s), serine proteinases (SVSP), and C-type lectins-like (CTL) proteins are major contributors to the geographic variability in venom. Principal component analyses demonstrate significant differences in venom composition between B. asper lineages previously identified through combination of molecular, morphological and geographical data, and provide additional insights into the selection pressures modulating venom phenotypes on a geographic scale. In particular, altitudinal zonation within the Andean mountain range stands out as a key ecological factor promoting diversification in venom. In addition, the pattern of distribution of PLA2 molecules among B. asper venoms complements phylogenetic analysis in the reconstruction of the dispersal events that account for the current biogeographic distribution of the present-day species' phylogroups. Ontogenic variation was also evident among venoms from some Ecuadorian lineages, although this age-related variation was less extreme than reported in B. asper venoms from Costa Rica. The results of our study demonstrate a significant impact of phylogenetic history on venom composition in a pitviper and show how analyses of this variation can illuminate the timing of the cladogenesis and ecological events that shaped the current distribution of B. asper lineages. Bothrops asper, called “the ultimate pitviper” due to its defensive behavior, large body size, and medical importance, represents a species complex that is widely distributed from southern México southwards across north‐western South America to north-western Perú. This work reports the characterization of the venom proteomes of B. asper lineages from the Pacific sides of Ecuador and south-western Colombia. Multivariate analyses indicate that variability in venom composition among the B. asper lineages is driven by proteins from four major toxin families, presumably in response to selection pressures created by recent and historical ecological conditions created by geological and climatic events from the Pliocene-Pleistocene to the present along the Central and South American Continental Divide. The emerging biogeographic pattern of venom variation, interpreted in the context of the current phylogenetic hypotheses, support and complement previously proposed evolutionary Plio-Pleistocene dispersal events that shaped the present-day distribution range of B. asper lineages. In addition, our venomics data indicate the occurrence of genetic exchange between Colombian and Pacific Costa Rican populations, which may have occurred during the second wave of B. asper migration into Mesoamerica. Our work represents a foundation for a future broader sampling and more complete “-omics” analyses to deepen our understanding of the patterns and causes of venom variation in this medically important pitviper.

ACS Style

Diana Mora-Obando; David Salazar-Valenzuela; Davinia Pla; Bruno Lomonte; Jimmy Alexander Guerrero-Vargas; Santiago Ayerbe; H. Lisle Gibbs; Juan J. Calvete. Venom variation in Bothrops asper lineages from North-Western South America. Journal of Proteomics 2020, 229, 103945 .

AMA Style

Diana Mora-Obando, David Salazar-Valenzuela, Davinia Pla, Bruno Lomonte, Jimmy Alexander Guerrero-Vargas, Santiago Ayerbe, H. Lisle Gibbs, Juan J. Calvete. Venom variation in Bothrops asper lineages from North-Western South America. Journal of Proteomics. 2020; 229 ():103945.

Chicago/Turabian Style

Diana Mora-Obando; David Salazar-Valenzuela; Davinia Pla; Bruno Lomonte; Jimmy Alexander Guerrero-Vargas; Santiago Ayerbe; H. Lisle Gibbs; Juan J. Calvete. 2020. "Venom variation in Bothrops asper lineages from North-Western South America." Journal of Proteomics 229, no. : 103945.

Research article
Published: 18 July 2020 in Journal of Proteome Research
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We report a structural and functional proteomics characterization of the venoms of the two subspecies (bilineatus and smaragdinus) of the South American palm pitviper B. bilineatus from the Brazilian state of Rondônia and B. b. smaragdinus from Perú. These poorly known arboreal and mostly nocturnal generalist predators are widely distributed in lowland rain forest throughout the entire Amazon region, where they represent an important cause of snakebites. The three B. bilineatus spp venom sampled exhibit overall conserved proteomic profiles comprising components belonging to 11 venom protein classes, with PIII (34-40% of the total venom proteins) and PI (8-18%) SVMPs and their endogenous tripeptide inhibitors (SVMPi, 8-10%); bradykinin-potentiating-like peptides (BBPs, 10.7-15%); snake venom serine proteinases (SVSP, 5.5-14%); C-type lectin-like proteins (CTL, 3-10%); phospholipases A2 (PLA2, 2.8-7.6%); cysteine-rich secretory proteins (CRISP, 0.9-2.8%); L-amino acid oxidases (LAO, 0.9-5%) representing the major components of their common venom proteomes. Comparative analysis of the venom proteomes of the two geographic variants of B. b. smaragdinus with that of B. b. bilineatus revealed that the two Brazilian taxa share identical molecules between themselves but not with Peruvian B. b. smaragdinus, suggesting hybridization between the geographically close, possibly sympatric, Porto Velho (RO, BR) B. b. smaragdinus and B. b. bilineatus parental populations. The toxin arsenal of the South American palm pitvipers may account for the in vitro recorded collagenolytic, caseinolytic, PLA2, L-amino acid oxidase, thrombin-like and factor X-activating activities, and the clinical features of South American palm pitviper envenomings, i.e. local and progressively ascending pain, shock and loss of consciousness, spontaneous bleeding and profound coagulopathy. The remarkable crossreactivity of the Brazilian pentabothropic SAB antivenom toward the heterologous B. b. bilineatus venom suggests that the paraspecific antigenic determinants should had been already present in the venom of the last common ancestor of the Bothrops "jararaca" and "taeniatus" clades, an event that has been dated about 8.5 Mya in the mid-late Miocene epoch of the Cenozoic era.

ACS Style

Libia Sanz; Sarai Quesada-Bernat; Alicia Pérez; Karen De Morais-Zani; Savio S. Sant' Anna; Daniela M. Hatakeyama; Lidia J. Tasima; Moisés B. De Souza; Anderson M. Kayano; Alfonso Zavaleta; Maria Salas; Andreimar M. Soares; Leonardo De A. Calderón; Anita M. Tanaka-Azevedo; Bruno Lomonte; Juan J. Calvete; Cleópatra A. S. Caldeira. Danger in the Canopy. Comparative Proteomics and Bioactivities of the Venoms of the South American Palm Pit Viper Bothrops bilineatus Subspecies bilineatus and smaragdinus and Antivenomics of B. b. bilineatus (Rondônia) Venom against the Brazilian Pentabothropic Antivenom. Journal of Proteome Research 2020, 19, 3518 -3532.

AMA Style

Libia Sanz, Sarai Quesada-Bernat, Alicia Pérez, Karen De Morais-Zani, Savio S. Sant' Anna, Daniela M. Hatakeyama, Lidia J. Tasima, Moisés B. De Souza, Anderson M. Kayano, Alfonso Zavaleta, Maria Salas, Andreimar M. Soares, Leonardo De A. Calderón, Anita M. Tanaka-Azevedo, Bruno Lomonte, Juan J. Calvete, Cleópatra A. S. Caldeira. Danger in the Canopy. Comparative Proteomics and Bioactivities of the Venoms of the South American Palm Pit Viper Bothrops bilineatus Subspecies bilineatus and smaragdinus and Antivenomics of B. b. bilineatus (Rondônia) Venom against the Brazilian Pentabothropic Antivenom. Journal of Proteome Research. 2020; 19 (8):3518-3532.

Chicago/Turabian Style

Libia Sanz; Sarai Quesada-Bernat; Alicia Pérez; Karen De Morais-Zani; Savio S. Sant' Anna; Daniela M. Hatakeyama; Lidia J. Tasima; Moisés B. De Souza; Anderson M. Kayano; Alfonso Zavaleta; Maria Salas; Andreimar M. Soares; Leonardo De A. Calderón; Anita M. Tanaka-Azevedo; Bruno Lomonte; Juan J. Calvete; Cleópatra A. S. Caldeira. 2020. "Danger in the Canopy. Comparative Proteomics and Bioactivities of the Venoms of the South American Palm Pit Viper Bothrops bilineatus Subspecies bilineatus and smaragdinus and Antivenomics of B. b. bilineatus (Rondônia) Venom against the Brazilian Pentabothropic Antivenom." Journal of Proteome Research 19, no. 8: 3518-3532.

Journal article
Published: 04 July 2020 in Toxicon
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The South American rattlesnake Crotalus durissus spp has a wide geographic distribution in Brazil. Although responsible for only a low proportion of ophidian accidents, it is considered one of the most medically important species of venomous snakes due to the high mortality rate (1.87%). Snake venom is a complex phenotype commonly subjected to individual intraspecific, ontogenetic and geographic variability. Compositional differences in pooled venom used in the immunization process may impact the efficacy of the antivenom. In order to assure standardized high-quality antivenom, the potency of each Brazilian crotalic antivenom batch is determined against the ‘Brazilian Crotalic Reference Venom’ (BCRV). BCRV is produced by Instituto Butantan using venom obtained from the first milking of recently wild-caught C. d. terrificus specimens brought to the Institute. The decrease in the number of snake donations experienced in recent years can become a threat to the production of future batches of BCRV. To evaluate the feasibility of using venom from long-term captive animals in the formulation of BCRV, we have compared the proteomic, biochemical and biological profiles of C. d. terrificus venom pooled from captive specimens (CVP- captive venom pool) and BCRV. Electrophoretic and venomics analyses revealed a very similar venom composition profile, but also certain differences in toxins abundance, with some low abundant protein families found only in BCRV. Enzymatic (L-amino acid oxidase, phospholipase A2 and proteolytic) and biological (myotoxic and coagulant) activities showed higher values in CVP than in BCRV. CVP also possessed slightly higher lethal effect, although the Instituto Butantan crotalic antivenom showed equivalent potency neutralizing BCRV and CVP. Our results strongly suggest that venom from long-term captive C. d. terrificus might be a valid alternative to generate an immunization mixture of equivalent quality to the currently in use reference venom.

ACS Style

Lidia J. Tasima; Daniela M. Hatakeyama; Caroline Serino-Silva; Caroline F.B. Rodrigues; Eduardo O.V. de Lima; Sávio S. Sant’Anna; Kathleen F. Grego; Karen de Morais-Zani; Libia Sanz; Juan J. Calvete; Anita M. Tanaka-Azevedo. Comparative proteomic profiling and functional characterization of venom pooled from captive Crotalus durissus terrificus specimens and the Brazilian crotalic reference venom. Toxicon 2020, 185, 26 -35.

AMA Style

Lidia J. Tasima, Daniela M. Hatakeyama, Caroline Serino-Silva, Caroline F.B. Rodrigues, Eduardo O.V. de Lima, Sávio S. Sant’Anna, Kathleen F. Grego, Karen de Morais-Zani, Libia Sanz, Juan J. Calvete, Anita M. Tanaka-Azevedo. Comparative proteomic profiling and functional characterization of venom pooled from captive Crotalus durissus terrificus specimens and the Brazilian crotalic reference venom. Toxicon. 2020; 185 ():26-35.

Chicago/Turabian Style

Lidia J. Tasima; Daniela M. Hatakeyama; Caroline Serino-Silva; Caroline F.B. Rodrigues; Eduardo O.V. de Lima; Sávio S. Sant’Anna; Kathleen F. Grego; Karen de Morais-Zani; Libia Sanz; Juan J. Calvete; Anita M. Tanaka-Azevedo. 2020. "Comparative proteomic profiling and functional characterization of venom pooled from captive Crotalus durissus terrificus specimens and the Brazilian crotalic reference venom." Toxicon 185, no. : 26-35.

Journal article
Published: 27 June 2020 in Journal of Proteomics
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The Duvernoy's gland secretory proteome of the false coral snake Rhinobothryum bovallii (Costa Rica), unveiled applying bottom-up venomics, comprises a handful of toxins belonging to only three protein families, three-finger toxin (3FTx), cysteine-rich secretory protein (CRISP), and snake venom metalloprotease (PIII-SVMP). Except for small differences in the relative abundance of the PIII-SVMPs, which may be due to individual variability, no evidence of geographic variability or ontogenetic changes was found among the venom proteomes of the juvenile and adult R. bovallii snakes sampled. Major monomeric (86.5%mol) and minor dimeric (2.8%mol) 3FTxs dominate the toxin arsenal of the Costa Rican false coral snake. The remaining 10.7% of the venom proteome comprises CRISP (8.2%) and PIII-SVMP (2.4%) molecules. In vivo lethality assays showed that R. bovallii produces venom that is non-toxic towards mammalian prey, and which exerts a different toxic effect on domestic chicken chicks and baby green iguana. Toxicovenomic analysis of R. bovallii venom in the iguana model identified two 3FTx RP-HPLC fractions that faithfully mimicked the irreversible immobilizing effect of the whole venom. With more than 2200 species in family Colubridae (sensu lato), rear-fanged snakes comprise approximately two-thirds of the extant species of advanced snakes. Snakebites from venomous snakes that are of medical concern are predominantly from front-fanged snakes of families Viperidae and Elapidae. On the other hand, rear-fanged snakes have been conventionally considered non-venomous, and thus their venoms have remained a largely untapped area of venomics. However, increasing documentation of life-threadening, even fatal, envenomings from rear-fanged snakes has sparked interest in their venoms. Appying bottom-up venomics we have revealed that the Duvernoy's gland secretory proteome of R. bovallii comprises a handful of toxins belonging to only three protein families, with slow-acting three-finger toxins (3FTx) that are non-toxic towards mammalian prey and show preference towards diapsid taxa representing the dominant structural and functional proteins. Our work documents for the first time 3FTxs exerting different effect in an avian model than in a reptile model. Besides, the 3FTx fractions that faithfully mimicked the irreversible iguana-immobilizing effect of the whole venom were identified through toxicovenomic analysis of R. bovallii venom on Iguana iguana. Our work underscores the importance of using biologically-relevant animal toxicity models for investigating the biological roles of venoms in an evolutionary-ecological context.

ACS Style

Juan J. Calvete; Fabián Bonilla; Sofía Granados-Martínez; Libia Sanz; Bruno Lomonte; Mahmood Sasa. Venomics of the Duvernoy's gland secretion of the false coral snake Rhinobothryum bovallii (Andersson, 1916) and assessment of venom lethality towards synapsid and diapsid animal models. Journal of Proteomics 2020, 225, 103882 .

AMA Style

Juan J. Calvete, Fabián Bonilla, Sofía Granados-Martínez, Libia Sanz, Bruno Lomonte, Mahmood Sasa. Venomics of the Duvernoy's gland secretion of the false coral snake Rhinobothryum bovallii (Andersson, 1916) and assessment of venom lethality towards synapsid and diapsid animal models. Journal of Proteomics. 2020; 225 ():103882.

Chicago/Turabian Style

Juan J. Calvete; Fabián Bonilla; Sofía Granados-Martínez; Libia Sanz; Bruno Lomonte; Mahmood Sasa. 2020. "Venomics of the Duvernoy's gland secretion of the false coral snake Rhinobothryum bovallii (Andersson, 1916) and assessment of venom lethality towards synapsid and diapsid animal models." Journal of Proteomics 225, no. : 103882.

Original article
Published: 27 June 2020 in Molecular Ecology
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Understanding how interspecific interactions mould the molecular basis of adaptations in coevolving species is a long‐sought goal of evolutionary biology. Venom in predators and venom resistance proteins in prey are coevolving molecular phenotypes, and while venoms are highly complex mixtures it is unclear if prey respond with equally complex resistance traits. Here we use a novel molecular methodology based on protein affinity columns to capture and identify candidate blood serum resistance proteins (‘Venom Interactive Proteins’ – VIPs) in California Ground Squirrels (Otospermophilus beecheyi ) that interact with venom proteins from their main predator, Northern Pacific Rattlesnakes (Crotalus o. oreganus ). This assay showed that serum‐based resistance is both population‐ and species‐specific, with serum proteins from ground squirrels showing higher binding affinities for venom proteins of local snakes compared to allopatric individuals. Venom protein specificity assays identified numerous and diverse candidate prey resistance VIPs but also potential targets of venom in prey tissues. Many specific VIPs bind to multiple snake venom proteins and, conversely, single venom proteins bind multiple VIPs, demonstrating that a portion of the squirrel blood serum “resistome” involves broad‐based inhibition of non‐self proteins and suggests that resistance involves a toxin scavenging mechanism. Analyses of rates of evolution of VIP protein homologs in related mammals show that most of these proteins evolve under purifying selection possibly due to molecular constraints that limit the evolutionary responses of prey to rapidly evolving snake venom proteins. Our method represents a general approach to identify specific proteins involved in coevolutionary interactions between species at the molecular level.

ACS Style

H. Lisle Gibbs; Libia Sanz; Alicia Pérez; Alexander Ochoa; Alyssa T.B. Hassinger; Matthew L. Holding; Juan J. Calvete. The molecular basis of venom resistance in a rattlesnake‐squirrel predator‐prey system. Molecular Ecology 2020, 29, 2871 -2888.

AMA Style

H. Lisle Gibbs, Libia Sanz, Alicia Pérez, Alexander Ochoa, Alyssa T.B. Hassinger, Matthew L. Holding, Juan J. Calvete. The molecular basis of venom resistance in a rattlesnake‐squirrel predator‐prey system. Molecular Ecology. 2020; 29 (15):2871-2888.

Chicago/Turabian Style

H. Lisle Gibbs; Libia Sanz; Alicia Pérez; Alexander Ochoa; Alyssa T.B. Hassinger; Matthew L. Holding; Juan J. Calvete. 2020. "The molecular basis of venom resistance in a rattlesnake‐squirrel predator‐prey system." Molecular Ecology 29, no. 15: 2871-2888.

Journal article
Published: 07 June 2020 in Journal of Proteomics
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We report a structural and functional venomics characterization of the black-tailed horned pitviper, Mixcoatlus melanurus. The venom phenotype of this small and elusive pitviper endemic to México comprise peptides and proteins of 16 toxin families whose relative abundance mirror those of neurotoxic (type II) venoms described for some species within genera distributed in Central Asia (Gloydius) and the Americas (Sistrurus, Crotalus, Ophryacus, and Bothriechis). A novel β-neurotoxic heterodimeric PLA2, termed Melanurutoxin was characterized. With a relative abundance of 14.8% of the total M. melanurus venom proteome and a median lethal dose of 0.31 μg/g mouse body weight, Melanurutoxin accounted for 37.8% of the lethality of the whole venom (0.82 μg/g). The low percentage (1.1%) of snake venom metalloproteinases (PIII-SVMPs) and the high content of Melanurutoxin and bradykinin-potentiating peptides (BPP, 16%) found in the type-II venom proteome of M. melanurus correlate with the severe hypotension and neurotoxicity leading to neuromuscular blockade, flaccid paralysis and respiratory arrest observed in ex vivo neuromuscular junction experiments and in vivo experimental murine envenoming. Mexican antivenoms manufactured by Birmex and Bioclon showed low neutralization potency per vial (95 LD50s, Birmex; 114 LD50s, Antivipmyn®), and failed to reverse completely the paralysis and the hypotensive effect induced by the black-tailed horned pitviper, Mixcoatlus melanurus. We suggest that the impaired ability of these antivenoms to neutralize the neurotoxicity of M. melanurus venom may be attributed to the use of immunization mixtures that include venom of taxa, C. basiliscus (Birmex) and C. simus (Antivipmyn®), that contain only small amounts of Melanurutoxin-like β-neurotoxic heterodimeric PLA2s. This study represents the first proteomics and funcional investigations conducted on the venom of the black-tailed horned, Mixcoatlus melanurus, a pitviper species endemic to México. The venom's features unveiled through combination of bottom-up venomics and ex vivo and in vivo functional assays provided complementary evidence pointing to severe hypotension and neurotoxicity leading to neuromuscular blockade, flaccid paralysis and respiratory arrest as the predominant mechanism of murine prey immobilization and death caused by M. melanurus. A novel β-neurotoxic heterodimeric PLA2, coined Melanurutoxin, was identified as a major contributor to the lethality of the whole venom. Our study also showed the inefficacy of two commercial Mexican antivenoms to reverse competely the paralytic and hypotensive effects induced by M. melanurus venom in the murine model. We hypothesize that the impaired ability of these antivenoms to neutralize the neurotoxicity of M. melanurus venom should be ascribed to the use as immunogens of venoms that contain only small amounts of Melanurutoxin-like β-neurotoxic heterodimeric PLA2s.

ACS Style

Edgar Neri-Castro; Libia Sanz; Alejandro Olvera-Rodríguez; Melisa Bénard-Valle; Alejandro Alagón; Juan J. Calvete. Venomics and biochemical analysis of the black-tailed horned pitviper, Mixcoatlus melanurus, and characterization of Melanurutoxin, a novel crotoxin homolog. Journal of Proteomics 2020, 225, 103865 .

AMA Style

Edgar Neri-Castro, Libia Sanz, Alejandro Olvera-Rodríguez, Melisa Bénard-Valle, Alejandro Alagón, Juan J. Calvete. Venomics and biochemical analysis of the black-tailed horned pitviper, Mixcoatlus melanurus, and characterization of Melanurutoxin, a novel crotoxin homolog. Journal of Proteomics. 2020; 225 ():103865.

Chicago/Turabian Style

Edgar Neri-Castro; Libia Sanz; Alejandro Olvera-Rodríguez; Melisa Bénard-Valle; Alejandro Alagón; Juan J. Calvete. 2020. "Venomics and biochemical analysis of the black-tailed horned pitviper, Mixcoatlus melanurus, and characterization of Melanurutoxin, a novel crotoxin homolog." Journal of Proteomics 225, no. : 103865.

Journal article
Published: 30 May 2020 in Toxicon: X
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Snake species within the Bothrops complex (sensu lato) are of medical relevance in Latin America, but knowledge on their venom characteristics is limited, or even unavailable, for some taxa. Perú harbors 17 species of pit vipers, within the genera Bothrops, Bothriechis, Bothrocophias, Porthidium, Crotalus, and Lachesis. This study compared the venoms of twelve species, through chromatographic and electrophoretic profiles, as well as proteolytic and phospholipase A2 (PLA2) activities. Also, proteomic profiles were analyzed for nine of the venoms using a shotgun approach. Results unveiled conspicuous differences in the expression of venom PLA2s among species, six of them presenting scarce levels as judged by RP-HPLC profiles. Since most species within the bothropoid lineage possess venoms with high to intermediate abundances of this protein family, our findings suggest the existence of a phenotypic duality in the expression of venom PLA2s within the Bothrops (sensu lato) complex. Bothrops barnetti and Bothrocophias andianus venoms, very scarce in PLA2s, were shown to lack significant myotoxic activity, highlighting that the observed variability in PLA2 expression bears toxicological correlations with effects attributed to these proteins. Finally, an attempt to identify phylogenetic relationships of bothropoid species from Perú presenting low- or high-PLA2 venom phenotypes showed an interspersed pattern, thus precluding a simple phylogenetic interpretation of this venom compositional dichotomy.

ACS Style

Bruno Lomonte; Cecilia Díaz; Fernando Chaves; Julián Fernández; Marco Ruiz; María Salas; Alfonso Zavaleta; Juan J. Calvete; Mahmood Sasa. Comparative characterization of Viperidae snake venoms from Perú reveals two compositional patterns of phospholipase A2 expression. Toxicon: X 2020, 7, 100044 .

AMA Style

Bruno Lomonte, Cecilia Díaz, Fernando Chaves, Julián Fernández, Marco Ruiz, María Salas, Alfonso Zavaleta, Juan J. Calvete, Mahmood Sasa. Comparative characterization of Viperidae snake venoms from Perú reveals two compositional patterns of phospholipase A2 expression. Toxicon: X. 2020; 7 ():100044.

Chicago/Turabian Style

Bruno Lomonte; Cecilia Díaz; Fernando Chaves; Julián Fernández; Marco Ruiz; María Salas; Alfonso Zavaleta; Juan J. Calvete; Mahmood Sasa. 2020. "Comparative characterization of Viperidae snake venoms from Perú reveals two compositional patterns of phospholipase A2 expression." Toxicon: X 7, no. : 100044.

Research article
Published: 06 May 2020 in Science Translational Medicine
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Snakebite envenoming causes 138,000 deaths annually, and ~400,000 victims are left with permanent disabilities. Envenoming by saw-scaled vipers (Viperidae: Echis) leads to systemic hemorrhage and coagulopathy and represents a major cause of snakebite mortality and morbidity in Africa and Asia. The only specific treatment for snakebite, antivenom, has poor specificity and low affordability and must be administered in clinical settings because of its intravenous delivery and high rates of adverse reactions. This requirement results in major treatment delays in resource-poor regions and substantially affects patient outcomes after envenoming. Here, we investigated the value of metal ion chelators as prehospital therapeutics for snakebite. Among the tested chelators, dimercaprol (British anti-Lewisite) and its derivative 2,3-dimercapto-1-propanesulfonic acid (DMPS) were found to potently antagonize the activity of Zn2+-dependent snake venom metalloproteinases in vitro. Moreover, DMPS prolonged or conferred complete survival in murine preclinical models of envenoming against a variety of saw-scaled viper venoms. DMPS also considerably extended survival in a “challenge and treat” model, where drug administration was delayed after venom injection and the oral administration of this chelator provided partial protection against envenoming. Last, the potential clinical scenario of early oral DMPS therapy combined with a delayed, intravenous dose of conventional antivenom provided prolonged protection against the lethal effects of envenoming in vivo. Our findings demonstrate that the safe and affordable repurposed metal chelator DMPS can effectively neutralize saw-scaled viper venoms in vitro and in vivo and highlight the promise of this drug as an early, prehospital, therapeutic intervention for hemotoxic snakebite envenoming.

ACS Style

Laura-Oana Albulescu; Melissa S. Hale; Stuart Ainsworth; Jaffer Alsolaiss; Edouard Crittenden; Juan J. Calvete; Chloe Evans; Mark C. Wilkinson; Robert A. Harrison; Jeroen Kool; Nicholas R. Casewell. Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite. Science Translational Medicine 2020, 12, eaay8314 .

AMA Style

Laura-Oana Albulescu, Melissa S. Hale, Stuart Ainsworth, Jaffer Alsolaiss, Edouard Crittenden, Juan J. Calvete, Chloe Evans, Mark C. Wilkinson, Robert A. Harrison, Jeroen Kool, Nicholas R. Casewell. Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite. Science Translational Medicine. 2020; 12 (542):eaay8314.

Chicago/Turabian Style

Laura-Oana Albulescu; Melissa S. Hale; Stuart Ainsworth; Jaffer Alsolaiss; Edouard Crittenden; Juan J. Calvete; Chloe Evans; Mark C. Wilkinson; Robert A. Harrison; Jeroen Kool; Nicholas R. Casewell. 2020. "Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite." Science Translational Medicine 12, no. 542: eaay8314.

Journal article
Published: 20 April 2020 in Toxicon: X
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We have applied a combination of venomics, in vivo neutralization assays, and in vitro third-generation antivenomics analysis to assess the preclinical efficacy of the monospecific anti-Macrovipera lebetina turanica (anti-Mlt) antivenom manufactured by Uzbiopharm® (Uzbekistan) and the monospecific anti-Vipera berus berus antivenom from Microgen® (Russia) against the venom of Dagestan blunt-nosed viper, Macrovipera lebetina obtusa (Mlo). Despite their low content of homologous (anti-Mlt, 5–10%) or para-specific (anti-Vbb, 4–9%) F(ab')2 antibody fragments against M. l. obtusa venom toxins, both antivenoms efficiently recognized most components of the complex venom proteome's arsenal, which is made up of toxins derived from 11 different gene families and neutralized, albeit at different doses, key toxic effects of M. l. obtusa venom, i.e., in vivo lethal and hemorrhagic effects in a murine model, and in vitro phospholipase A2, proteolytic and coagulant activities. The calculated lethality neutralization potencies for Uzbiopharm® anti-Mlt and anti-Vbb Microgen® antivenoms were 1.46 and 1.77 mg/mL, indicating that 1 mL of Uzbiopharm® and Microgen® antivenoms may protect mice from 41 to 50 LD50s of Mlo venom, respectively. The remarkable degree of conservation of immunogenic determinants between species of the clades of European and Oriental viper, which evolved geographically segregated since the early Miocene, suggests an eventual window of opportunity for the treatment of envenomings by Eurasian snakes. Clearly, the rational use of heterologous antivenoms requires establishing their para-specificity landscapes. This paper illustrates the analytical power of combining in vitro and in vivo preclinical quantitative assays toward this goal.

ACS Style

Davinia Pla; Sarai Quesada-Bernat; Yania Rodríguez; Andrés Sánchez; Mariángela Vargas; Mauren Villalta; Susana Mesén; Álvaro Segura; Denis O. Mustafin; Yulia A. Fomina; Ruslan I. Al-Shekhadat; Juan J. Calvete. Dagestan blunt-nosed viper, Macrovipera lebetina obtusa (Dwigubsky, 1832), venom. Venomics, antivenomics, and neutralization assays of the lethal and toxic venom activities by anti-Macrovipera lebetina turanica and anti-Vipera berus berus antivenoms. Toxicon: X 2020, 6, 100035 .

AMA Style

Davinia Pla, Sarai Quesada-Bernat, Yania Rodríguez, Andrés Sánchez, Mariángela Vargas, Mauren Villalta, Susana Mesén, Álvaro Segura, Denis O. Mustafin, Yulia A. Fomina, Ruslan I. Al-Shekhadat, Juan J. Calvete. Dagestan blunt-nosed viper, Macrovipera lebetina obtusa (Dwigubsky, 1832), venom. Venomics, antivenomics, and neutralization assays of the lethal and toxic venom activities by anti-Macrovipera lebetina turanica and anti-Vipera berus berus antivenoms. Toxicon: X. 2020; 6 ():100035.

Chicago/Turabian Style

Davinia Pla; Sarai Quesada-Bernat; Yania Rodríguez; Andrés Sánchez; Mariángela Vargas; Mauren Villalta; Susana Mesén; Álvaro Segura; Denis O. Mustafin; Yulia A. Fomina; Ruslan I. Al-Shekhadat; Juan J. Calvete. 2020. "Dagestan blunt-nosed viper, Macrovipera lebetina obtusa (Dwigubsky, 1832), venom. Venomics, antivenomics, and neutralization assays of the lethal and toxic venom activities by anti-Macrovipera lebetina turanica and anti-Vipera berus berus antivenoms." Toxicon: X 6, no. : 100035.

Conference abstract
Published: 01 April 2020 in Toxicon
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ACS Style

Libia Sanz; Lucas N. De Freitas-Lima; Sarai Quesada-Bernat; Viviane K. Graça-De-Souza; Andreimar M. Soares; Leonardo De A. Calderón; Juan Calvete; Cleópatra A.S. Caldeira. Comparative venomics of Brazilian coral snakes: Micrurus frontalis, Micrurus spixii spixii, and Micrurus surinamensis. Toxicon 2020, 177, S20 .

AMA Style

Libia Sanz, Lucas N. De Freitas-Lima, Sarai Quesada-Bernat, Viviane K. Graça-De-Souza, Andreimar M. Soares, Leonardo De A. Calderón, Juan Calvete, Cleópatra A.S. Caldeira. Comparative venomics of Brazilian coral snakes: Micrurus frontalis, Micrurus spixii spixii, and Micrurus surinamensis. Toxicon. 2020; 177 ():S20.

Chicago/Turabian Style

Libia Sanz; Lucas N. De Freitas-Lima; Sarai Quesada-Bernat; Viviane K. Graça-De-Souza; Andreimar M. Soares; Leonardo De A. Calderón; Juan Calvete; Cleópatra A.S. Caldeira. 2020. "Comparative venomics of Brazilian coral snakes: Micrurus frontalis, Micrurus spixii spixii, and Micrurus surinamensis." Toxicon 177, no. : S20.

Conference abstract
Published: 01 April 2020 in Toxicon
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ACS Style

H. Lisle Gibbs; Libia Sanz; Alicia Pérez; Alexander Ochoa; Alyssa Tb. Hassinger; Matthew L. Holding; Juan Calvete. The molecular basis of venom resistance in a rattlesnake-squirrel predator-prey system. Toxicon 2020, 177, S46 .

AMA Style

H. Lisle Gibbs, Libia Sanz, Alicia Pérez, Alexander Ochoa, Alyssa Tb. Hassinger, Matthew L. Holding, Juan Calvete. The molecular basis of venom resistance in a rattlesnake-squirrel predator-prey system. Toxicon. 2020; 177 ():S46.

Chicago/Turabian Style

H. Lisle Gibbs; Libia Sanz; Alicia Pérez; Alexander Ochoa; Alyssa Tb. Hassinger; Matthew L. Holding; Juan Calvete. 2020. "The molecular basis of venom resistance in a rattlesnake-squirrel predator-prey system." Toxicon 177, no. : S46.

Conference abstract
Published: 01 April 2020 in Toxicon
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ACS Style

Edgar Neri-Castro; Melisa Bénard-Valle; Irving Archundia; Juan Calvete; Alejandro Alagón. Implications of snake venom variation on antivenom neutralization: The case of North American vipers. Toxicon 2020, 177, S25 .

AMA Style

Edgar Neri-Castro, Melisa Bénard-Valle, Irving Archundia, Juan Calvete, Alejandro Alagón. Implications of snake venom variation on antivenom neutralization: The case of North American vipers. Toxicon. 2020; 177 ():S25.

Chicago/Turabian Style

Edgar Neri-Castro; Melisa Bénard-Valle; Irving Archundia; Juan Calvete; Alejandro Alagón. 2020. "Implications of snake venom variation on antivenom neutralization: The case of North American vipers." Toxicon 177, no. : S25.