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Robert A. Harrison - One of the best experts on this subject based on the ideXlab platform.
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Concerns over an antivenom widely marketed in sub-Saharan Africa.
2017Co-Authors: Robert A. Harrison, José María Gutiérrez, George O. Oluoch, Stuart Ainsworth, Jaffer Alsolaiss, Fiona Bolton, Ana-silvia Arias, Paul Rowley, Stephen Kalya, Hastings OzwaraAbstract:Why are venoms from the Asian Russell’s viper (Daboia russelii—incorrectly labelled here as Vipera russelli) and saw-scaled viper (Echis carinatus) included in its efficacy statement?.
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cytotoxic activities of ser phospholipase a from the venom of the saw scaled vipers Echis ocellatus Echis pyramidum leakeyi Echis carinatus sochureki and Echis coloratus
Toxicon, 2013Co-Authors: Michael J Conlon, Nicholas R Casewell, Robert A. Harrison, Samir Attoub, Hama Arafat, Milena Mechkarska, Juan J. CalveteAbstract:Fractionation by reversed-phase HPLC of venom from four species of saw-scaled viper: Echis ocellatus, Echis pyramidum leakeyi, Echis carinatus sochureki, and Echis coloratus led to identification in each sample of an abundant protein with cytotoxic activity against human non-small cell lung adenocarcinoma A549 cells. The active component in each case was identified by MALDI-TOF mass fingerprinting of tryptic digests as [Ser⁴⁹]phospholipase A₂ ([Ser⁴⁹]PLA₂). An isoform of [Ser⁴⁹]PLA₂ containing the single Ala¹⁸→ Val substitution and a partially characterized [Asp⁴⁹]PLA₂ were also present in the E. coloratus venom. LC₅₀ values against A549 cells for the purified [Ser⁴⁹]PLA₂ proteins from the four species are in the range 2.9-8.5 μM. This range is not significantly different from the range of LC₅₀ values against human umbilical vein endothelial HUVEC cells (2.5-12.2 μM) indicating that the [Ser⁴⁹]PLA₂ proteins show no differential anti-tumor activity. The LC₅₀ value for [Ser⁴⁹]PLA₂ from E. ocellatus against human erythrocytes is >100 μM and the MIC values against Escherichia coli and Staphylococcus aureus are >100 μM. It is suggested that the [Ser⁴⁹]PLA₂ proteins play a major role in producing local tissue necrosis and hemorrhage at the site of envenomation.
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Distribution of four Echis species in Africa and the Middle East.
2013Co-Authors: Nicholas R Casewell, Nandul Durfa, Wolfgang Wuster, Darren A N Cook, Simon C Wagstaff, Abdulsalami Nasidi, Robert A. HarrisonAbstract:Key: E. ocellatus – blue, E. pyramidum – red, E. coloratus – green, E. carinatus – purple. Distributions mapped according to the WHO venomous snake distribution database and a recent study of the genus Echis [16], [35].
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antivenomic assessment of the immunological reactivity of echitab plus icp an antivenom for the treatment of snakebite envenoming in sub saharan africa
American Journal of Tropical Medicine and Hygiene, 2010Co-Authors: Juan J. Calvete, Robert A. Harrison, Libia Sanz, Álvaro Segura, María Herrera, Mauren Villalta, Guillermo León, Nandul Durfa, Abdusalami Nasidi, David R G TheakstonAbstract:The immunoreactivity of EchiTAb-Plus-ICP, an antivenom developed for the treatment of snakebite envenoming in sub-Saharan Africa, to venoms of seven Echis and Bitis species, was assessed by "antivenomics." This proteomic approach is based on the ability of an antivenom to immunodeplete homologous or heterologous venom proteins. Our results show an extensive cross-reactivity of this antivenom against all Echis and Bitis venoms studied, as revealed by the complete immunodepletion of the majority of venom components, including metalloproteinases, serine proteinases, C-type lectin-like proteins, some phospholipases A(2) and L-amino acid oxidase. However, some phospholipases A(2), disintegrins and proteinase inhibitors were immunodepleted to only a partial extent. These results support the hypothesis that immunizing horses with a mixture of the venoms of Echis ocellatus, Bitis arietans, and Naja nigricollis generates antibodies capable of recognizing the majority of components of medically-relevant homologous and heterologous viperid venoms of the genera Bitis and Echis from sub-Saharan Africa.
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preclinical assessment of the efficacy of a new antivenom echitab plus icp for the treatment of viper envenoming in sub saharan africa
Toxicon, 2010Co-Authors: Álvaro Segura, Robert A. Harrison, Juan J. Calvete, María Herrera, Mauren Villalta, Guillermo León, Nandul Durfa, Abdusalami Nasidi, David R G Theakston, David A. WarrellAbstract:A preclinical assessment was performed on the neutralizing efficacy of a whole IgG polyspecific antivenom (EchiTAb-Plus-ICP®), designed for the treatment of snakebite envenomings in Nigeria. It was generated by immunizing horses with the venoms of Echis ocellatus, Bitis arietans and Naja nigricollis, the most medically important species in Nigeria. Antivenom was tested against the venoms of E. ocellatus, Echis leucogaster, Echis pyramidum leakeyi, B. arietans, Bitis gabonica, Bitis rhinoceros and Bitis nasicornis. The neutralization of the venom toxins responsible for the lethal, hemorrhagic, coagulant and local necrotizing activities was assessed, since these are the most significant effects that characterize envenoming by these species. Echis sp venoms exerted lethal, hemorrhagic, coagulant and necrotizing effects, whereas the Bitis sp venoms tested induced lethality, hemorrhage and necrosis, but were devoid of coagulant activity. The antivenom was effective in the neutralization of all effects tested in all venoms. Highest neutralization was achieved against the venoms of E. ocellatus and B. arietans, and the lowest neutralizing potency was against the venom of B. nasicornis, a species that has a low clinical relevance. It is concluded that EchiTAb-Plus-ICP®, whilst specifically designed for Nigeria, has a good preclinical neutralizing profile against homologous and heterologous viperid venoms from other sub-Saharan African locations. It therefore constitutes a promising therapeutic option for the treatment of snakebite envenoming in this region.
Juan J. Calvete - One of the best experts on this subject based on the ideXlab platform.
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cytotoxic activities of ser phospholipase a from the venom of the saw scaled vipers Echis ocellatus Echis pyramidum leakeyi Echis carinatus sochureki and Echis coloratus
Toxicon, 2013Co-Authors: Michael J Conlon, Nicholas R Casewell, Robert A. Harrison, Samir Attoub, Hama Arafat, Milena Mechkarska, Juan J. CalveteAbstract:Fractionation by reversed-phase HPLC of venom from four species of saw-scaled viper: Echis ocellatus, Echis pyramidum leakeyi, Echis carinatus sochureki, and Echis coloratus led to identification in each sample of an abundant protein with cytotoxic activity against human non-small cell lung adenocarcinoma A549 cells. The active component in each case was identified by MALDI-TOF mass fingerprinting of tryptic digests as [Ser⁴⁹]phospholipase A₂ ([Ser⁴⁹]PLA₂). An isoform of [Ser⁴⁹]PLA₂ containing the single Ala¹⁸→ Val substitution and a partially characterized [Asp⁴⁹]PLA₂ were also present in the E. coloratus venom. LC₅₀ values against A549 cells for the purified [Ser⁴⁹]PLA₂ proteins from the four species are in the range 2.9-8.5 μM. This range is not significantly different from the range of LC₅₀ values against human umbilical vein endothelial HUVEC cells (2.5-12.2 μM) indicating that the [Ser⁴⁹]PLA₂ proteins show no differential anti-tumor activity. The LC₅₀ value for [Ser⁴⁹]PLA₂ from E. ocellatus against human erythrocytes is >100 μM and the MIC values against Escherichia coli and Staphylococcus aureus are >100 μM. It is suggested that the [Ser⁴⁹]PLA₂ proteins play a major role in producing local tissue necrosis and hemorrhage at the site of envenomation.
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antivenomic assessment of the immunological reactivity of echitab plus icp an antivenom for the treatment of snakebite envenoming in sub saharan africa
American Journal of Tropical Medicine and Hygiene, 2010Co-Authors: Juan J. Calvete, Robert A. Harrison, Libia Sanz, Álvaro Segura, María Herrera, Mauren Villalta, Guillermo León, Nandul Durfa, Abdusalami Nasidi, David R G TheakstonAbstract:The immunoreactivity of EchiTAb-Plus-ICP, an antivenom developed for the treatment of snakebite envenoming in sub-Saharan Africa, to venoms of seven Echis and Bitis species, was assessed by "antivenomics." This proteomic approach is based on the ability of an antivenom to immunodeplete homologous or heterologous venom proteins. Our results show an extensive cross-reactivity of this antivenom against all Echis and Bitis venoms studied, as revealed by the complete immunodepletion of the majority of venom components, including metalloproteinases, serine proteinases, C-type lectin-like proteins, some phospholipases A(2) and L-amino acid oxidase. However, some phospholipases A(2), disintegrins and proteinase inhibitors were immunodepleted to only a partial extent. These results support the hypothesis that immunizing horses with a mixture of the venoms of Echis ocellatus, Bitis arietans, and Naja nigricollis generates antibodies capable of recognizing the majority of components of medically-relevant homologous and heterologous viperid venoms of the genera Bitis and Echis from sub-Saharan Africa.
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preclinical assessment of the efficacy of a new antivenom echitab plus icp for the treatment of viper envenoming in sub saharan africa
Toxicon, 2010Co-Authors: Álvaro Segura, Robert A. Harrison, Juan J. Calvete, María Herrera, Mauren Villalta, Guillermo León, Nandul Durfa, Abdusalami Nasidi, David R G Theakston, David A. WarrellAbstract:A preclinical assessment was performed on the neutralizing efficacy of a whole IgG polyspecific antivenom (EchiTAb-Plus-ICP®), designed for the treatment of snakebite envenomings in Nigeria. It was generated by immunizing horses with the venoms of Echis ocellatus, Bitis arietans and Naja nigricollis, the most medically important species in Nigeria. Antivenom was tested against the venoms of E. ocellatus, Echis leucogaster, Echis pyramidum leakeyi, B. arietans, Bitis gabonica, Bitis rhinoceros and Bitis nasicornis. The neutralization of the venom toxins responsible for the lethal, hemorrhagic, coagulant and local necrotizing activities was assessed, since these are the most significant effects that characterize envenoming by these species. Echis sp venoms exerted lethal, hemorrhagic, coagulant and necrotizing effects, whereas the Bitis sp venoms tested induced lethality, hemorrhage and necrosis, but were devoid of coagulant activity. The antivenom was effective in the neutralization of all effects tested in all venoms. Highest neutralization was achieved against the venoms of E. ocellatus and B. arietans, and the lowest neutralizing potency was against the venom of B. nasicornis, a species that has a low clinical relevance. It is concluded that EchiTAb-Plus-ICP®, whilst specifically designed for Nigeria, has a good preclinical neutralizing profile against homologous and heterologous viperid venoms from other sub-Saharan African locations. It therefore constitutes a promising therapeutic option for the treatment of snakebite envenoming in this region.
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snake venom disintegrins novel dimeric disintegrins and structural diversification by disulphide bond engineering
Biochemical Journal, 2003Co-Authors: Juan J. Calvete, David R G Theakston, Paz M Morenomurciano, Dariusz G Kisiel, Cezary MarcinkiewiczAbstract:We report the isolation and amino acid sequences of six novel dimeric disintegrins from the venoms of Vipera lebetina obtusa (VLO), V. berus (VB), V. ammodytes (VA), Echis ocellatus (EO) and Echis multisquamatus (EMS). Disintegrins VLO4, VB7, VA6 and EO4 displayed the RGD motif and inhibited the adhesion of K562 cells, expressing the integrin alpha5beta1 to immobilized fibronectin. A second group of dimeric disintegrins (VLO5 and EO5) had MLD and VGD motifs in their subunits and blocked the adhesion of the alpha4beta1 integrin to vascular cell adhesion molecule 1 with high selectivity. On the other hand, disintegrin EMS11 inhibited both alpha5beta1 and alpha4beta1 integrins with almost the same degree of specificity. Comparison of the amino acid sequences of the dimeric disintegrins with those of other disintegrins by multiple-sequence alignment and phylogenetic analysis, in conjunction with current biochemical and genetic data, supports the view that the different disintegrin subfamilies evolved from a common ADAM (a disintegrin and metalloproteinase-like) scaffold and that structural diversification occurred through disulphide bond engineering.
Nicholas R Casewell - One of the best experts on this subject based on the ideXlab platform.
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differential procoagulant effects of saw scaled viper serpentes viperidae Echis snake venoms on human plasma and the narrow taxonomic ranges of antivenom efficacies
Toxicology Letters, 2017Co-Authors: Aymeric Rogalski, Christina N Zdenek, Bianca Op Den Brouw, Kevin Arbuckle, Christoffer Soerensen, Daniel Dashevsky, Alexandra Gloria, C. J. Lister, Nicholas R CasewellAbstract:Abstract Saw-scaled vipers (genus Echis ) are one of the leading causes of snakebite morbidity and mortality in parts of Sub-Saharan Africa, the Middle East, and vast regions of Asia, constituting a public health burden exceeding that of almost any other snake genus globally. Venom-induced consumption coagulopathy, owing to the action of potent procoagulant toxins, is one of the most relevant clinical manifestations of envenomings by Echis spp. Clinical experience and prior studies examining a limited range of venoms and restricted antivenoms have demonstrated for some antivenoms an extreme lack of antivenom cross-reactivity between different species of this genus, sometimes resulting in catastrophic treatment failure. This study undertook the most comprehensive testing of Echis venom effects upon the coagulation of human plasma, and also the broadest examination of antivenom potency and cross-reactivity, to-date. 10 Echis species/populations and four antivenoms (two African, two Asian) were studied. The results indicate that the venoms are, in general, potently procoagulant but that the relative dependence on calcium or phospholipid cofactors is highly variable. Additionally, three out of the four antivenoms tested demonstrated only a very narrow taxonomic range of effectiveness in preventing coagulopathy, with only the SAIMR antivenom displaying significant levels of cross-reactivity. These results were in conflict with previous studies using prolonged preincubation of antivenom with venom to suggest effective cross-reactivity levels for the ICP Echi-Tab antivenom. These findings both inform upon potential clinical effects of envenomation in humans and highlight the extreme limitations of available treatment. It is hoped that this will spur efforts into the development of antivenoms with more comprehensive coverage for bites not only from wild snakes but also from specimens widely kept in zoological collections.
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cytotoxic activities of ser phospholipase a from the venom of the saw scaled vipers Echis ocellatus Echis pyramidum leakeyi Echis carinatus sochureki and Echis coloratus
Toxicon, 2013Co-Authors: Michael J Conlon, Nicholas R Casewell, Robert A. Harrison, Samir Attoub, Hama Arafat, Milena Mechkarska, Juan J. CalveteAbstract:Fractionation by reversed-phase HPLC of venom from four species of saw-scaled viper: Echis ocellatus, Echis pyramidum leakeyi, Echis carinatus sochureki, and Echis coloratus led to identification in each sample of an abundant protein with cytotoxic activity against human non-small cell lung adenocarcinoma A549 cells. The active component in each case was identified by MALDI-TOF mass fingerprinting of tryptic digests as [Ser⁴⁹]phospholipase A₂ ([Ser⁴⁹]PLA₂). An isoform of [Ser⁴⁹]PLA₂ containing the single Ala¹⁸→ Val substitution and a partially characterized [Asp⁴⁹]PLA₂ were also present in the E. coloratus venom. LC₅₀ values against A549 cells for the purified [Ser⁴⁹]PLA₂ proteins from the four species are in the range 2.9-8.5 μM. This range is not significantly different from the range of LC₅₀ values against human umbilical vein endothelial HUVEC cells (2.5-12.2 μM) indicating that the [Ser⁴⁹]PLA₂ proteins show no differential anti-tumor activity. The LC₅₀ value for [Ser⁴⁹]PLA₂ from E. ocellatus against human erythrocytes is >100 μM and the MIC values against Escherichia coli and Staphylococcus aureus are >100 μM. It is suggested that the [Ser⁴⁹]PLA₂ proteins play a major role in producing local tissue necrosis and hemorrhage at the site of envenomation.
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Distribution of four Echis species in Africa and the Middle East.
2013Co-Authors: Nicholas R Casewell, Nandul Durfa, Wolfgang Wuster, Darren A N Cook, Simon C Wagstaff, Abdulsalami Nasidi, Robert A. HarrisonAbstract:Key: E. ocellatus – blue, E. pyramidum – red, E. coloratus – green, E. carinatus – purple. Distributions mapped according to the WHO venomous snake distribution database and a recent study of the genus Echis [16], [35].
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Pre-clinical assays predict pan-African Echis viper efficacy for a species-specific antivenom.
Public Library of Science (PLoS), 2010Co-Authors: Nicholas R Casewell, Nandul Durfa, Wolfgang Wuster, Darren A N Cook, Simon C Wagstaff, Abdulsalami Nasidi, Robert A. HarrisonAbstract:Snakebite is a significant cause of death and disability in subsistent farming populations of sub-Saharan Africa. Antivenom is the most effective treatment of envenoming and is manufactured from IgG of venom-immunised horses/sheep but, because of complex fiscal reasons, there is a paucity of antivenom in sub-Saharan Africa. To address the plight of thousands of snakebite victims in savannah Nigeria, the EchiTAb Study Group organised the production, testing and delivery of antivenoms designed to treat envenoming by the most medically-important snakes in the region. The Echis saw-scaled vipers have a wide African distribution and medical importance. In an effort to maximise the clinical utility of scarce antivenom resources in Africa, we aimed to ascertain, at the pre-clinical level, to what extent the E. ocellatus-specific EchiTAbG antivenom, which was designed specifically for Nigeria, neutralised the lethal activity of venom from two other African species, E. pyramidum leakeyi and E. coloratus.Despite apparently quite distinctive venom protein profiles, we observed extensive cross-species similarity in the immuno-reactivity profiles of Echis species-specific antisera. Using WHO standard pre-clinical in vivo tests, we determined that the monospecific EchiTAbG antivenom was as effective at neutralising the venom-induced lethal effects of E. pyramidum leakeyi and E. coloratus as it was against E. ocellatus venom. Under the restricted conditions of this assay, the antivenom was ineffective against the lethal effects of venom from the non-African Echis species, E. carinatus sochureki.Using WHO-recommended pre-clinical tests we have demonstrated that the new anti-E. ocellatus monospecific antivenom EchiTAbG, developed in response to the considerable snakebite-induced mortality and morbidity in Nigeria, neutralised the lethal effects of venoms from Echis species representing each taxonomic group of this genus in Africa. This suggests that this monospecific antivenom has potential to treat envenoming by most, perhaps all, African Echis species
Takashi Morita - One of the best experts on this subject based on the ideXlab platform.
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comparative biochemistry of disintegrins isolated from snake venom consideration of the taxonomy and geographical distribution of snakes in the genus Echis
Journal of Biochemistry, 2001Co-Authors: Daiju Okuda, Fujio Sekiya, Chihiro Nozaki, Takashi MoritaAbstract:Species in the genus Echis have been classified mainly based on their morphological appearance and the analytical patterns of their serum. However, re-classification of the genus Echis has recently been suggested by taxonomists, toxicologists, and clinicians, since there have been problems with the current classification, such as the efficacy of antivenoms used for treating bites and the broad geographical distribution of Echis snakes. In this study, we purified five novel disintegrins, the platelet aggregation inhibitors pyramidin A and B from the venom of Echis pyramidum, ocellatin from the venom of Echis ocellatus, and leucogastin A and B from the venom of Echis leucogaster, to compare their sequences and allow us to re-evaluate the classification of various species in the genus Echis. Comparison of the amino acid sequences of five new and four known isolated disintegrins from snake venoms of six Echis species and their distribution strongly support the recent re-classification of the genus Echis.
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Prothrombin and factor X activator activities in the venoms of Viperidae snakes
Toxicon, 1997Co-Authors: Daisuke Yamada, Fujio Sekiya, Takashi MoritaAbstract:A Ca2+-dependent prothrombin activator, carinactivase-1 (CA-1), was previously found in the venom of Echis carinatus leucogaster. In the present study, the activities of CA-1-like enzymes were screened in the venoms of various Viperidae snakes. The addition of 1 mM Ca2+ ions to the venoms of only Echis snakes in Viperidae produced considerably high prothrombin activator activity, indicating that only the Echis snake venoms contain not only the Ca2+-independent prothrombin activator, ecarin, but also Ca2+-dependent activator(s). CA-1-like activators and ecarin in the venom of each Echis snake were efficiently separated by Blue Sepharose column chromatography. The venoms of the various Viperidae snakes were also examined for factor X activator activity. The venoms of genera Daboia, Vipera, Cerastes, Echis, Calloselasma and Bothrops contained factor X activator activity in the presence of Ca2+ ions. Cerastes cerastes and Calloselasma rhodostoma venoms also had Ca2+-independent factor X activator activity.
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Purification and Characterization of a Ca2+-Dependent Prothrombin Activator, Multactivase, from the Venom of Echis multisquamatus
Journal of biochemistry, 1997Co-Authors: Daisuke Yamada, Takashi MoritaAbstract:We previously found a novel Ca2+-dependent prothrombin activator, designated as carinactivase-1, in Echis carinatus leucogaster venom [D. Yamada, F. Sekiya, and T. Morita (1996) J. Biol. Chem. 271, 5200-5207]. Of the Viperidae snake venoms examined, the Echis multisquamatus venom had the strongest carinactivase-like activity. We isolated and characterized the carinactivase-like prothrombin activator in E. multisquamatus venom. From 50 mg of E. multisquamatus venom, we isolated 2.3 mg of a Ca2+-dependent prothrombin activator designated as multactivase. Unlike other Echis snake venoms, the E. multisquamatus venom contained no ecarin-like Ca2+-independent prothrombin activator. The structure and function of multactivase are similar to those of carinactivase. Multactivase is composed of a catalytic subunit with metalloprotease activity and a regulatory subunit comprising two homologous polypeptides bound by S-S bridge(s), and it activates prothrombin via recognition of the Ca2+-bound conformation of its Gla domain. We developed a chromogenic assay involving multactivase for normal prothrombin activity in plasma from individuals orally administered anticoagulants. The normal prothrombin activity, as a percentage, measured with multactivase was highly correlated with the prothrombin time. Multactivase is useful for the simple quantification of normal prothrombin in plasma from warfarin-treated individuals.
Wolfgang Wuster - One of the best experts on this subject based on the ideXlab platform.
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Distribution of four Echis species in Africa and the Middle East.
2013Co-Authors: Nicholas R Casewell, Nandul Durfa, Wolfgang Wuster, Darren A N Cook, Simon C Wagstaff, Abdulsalami Nasidi, Robert A. HarrisonAbstract:Key: E. ocellatus – blue, E. pyramidum – red, E. coloratus – green, E. carinatus – purple. Distributions mapped according to the WHO venomous snake distribution database and a recent study of the genus Echis [16], [35].
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venom lethality and diet differential responses of natural prey and model organisms to the venom of the saw scaled vipers Echis
Toxicon, 2012Co-Authors: David P Richards, Axel Barlow, Wolfgang WusterAbstract:The composition of snake venoms shows a high degree of variation at all taxonomic levels, and natural selection for diet has been implicated as a potential cause. Saw-scaled vipers (Echis) provide a good model for studying this phenomenon. The venoms of arthropod feeding species of Echis are significantly more toxic to natural scorpion prey than those of species which feed predominantly upon vertebrate prey. Although testing venom activity on natural prey is important for our understanding of the evolution of venom, natural prey species are often difficult to obtain in sufficient numbers for toxinological work. In order to test the viability of using cheaper and more easily available model organisms for toxicity assessments in evolutionary research, and the extent to which toxicity of arthropod-eating Echis venoms is increased to arthropods in general or targeted to certain groups, we conducted median lethal dosage (LD(50)) and time to death trials using the desert locust (Schistocerca gregaria) as a model arthropod, rarely consumed by wild Echis. The venoms of arthropod specialist Echis were found to be significantly more toxic to locusts than the venom of a vertebrate feeding outgroup (Bitis arietans), and one arthropod specialist venom was found to be more toxic than those species which feed upon arthropods infrequently or not at all. The venoms of arthropod specialists were also found to cause death and incapacitation faster than the vertebrate feeding outgroup. Despite some similarity of trends, there are considerable differences between the response of natural prey (scorpions) and a model arthropod (locust) to the venoms of Echis species. This suggests that when possible, natural prey rather than convenient model organisms should be used to gain an understanding of the functional significance of variation in venom composition in snakes.
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Pre-clinical assays predict pan-African Echis viper efficacy for a species-specific antivenom.
Public Library of Science (PLoS), 2010Co-Authors: Nicholas R Casewell, Nandul Durfa, Wolfgang Wuster, Darren A N Cook, Simon C Wagstaff, Abdulsalami Nasidi, Robert A. HarrisonAbstract:Snakebite is a significant cause of death and disability in subsistent farming populations of sub-Saharan Africa. Antivenom is the most effective treatment of envenoming and is manufactured from IgG of venom-immunised horses/sheep but, because of complex fiscal reasons, there is a paucity of antivenom in sub-Saharan Africa. To address the plight of thousands of snakebite victims in savannah Nigeria, the EchiTAb Study Group organised the production, testing and delivery of antivenoms designed to treat envenoming by the most medically-important snakes in the region. The Echis saw-scaled vipers have a wide African distribution and medical importance. In an effort to maximise the clinical utility of scarce antivenom resources in Africa, we aimed to ascertain, at the pre-clinical level, to what extent the E. ocellatus-specific EchiTAbG antivenom, which was designed specifically for Nigeria, neutralised the lethal activity of venom from two other African species, E. pyramidum leakeyi and E. coloratus.Despite apparently quite distinctive venom protein profiles, we observed extensive cross-species similarity in the immuno-reactivity profiles of Echis species-specific antisera. Using WHO standard pre-clinical in vivo tests, we determined that the monospecific EchiTAbG antivenom was as effective at neutralising the venom-induced lethal effects of E. pyramidum leakeyi and E. coloratus as it was against E. ocellatus venom. Under the restricted conditions of this assay, the antivenom was ineffective against the lethal effects of venom from the non-African Echis species, E. carinatus sochureki.Using WHO-recommended pre-clinical tests we have demonstrated that the new anti-E. ocellatus monospecific antivenom EchiTAbG, developed in response to the considerable snakebite-induced mortality and morbidity in Nigeria, neutralised the lethal effects of venoms from Echis species representing each taxonomic group of this genus in Africa. This suggests that this monospecific antivenom has potential to treat envenoming by most, perhaps all, African Echis species
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when continents collide phylogeny historical biogeography and systematics of the medically important viper genus Echis squamata serpentes viperidae
Molecular Phylogenetics and Evolution, 2009Co-Authors: Catharine E Pook, Ulrich Joger, Nikolaus Stumpel, Wolfgang WusterAbstract:We analyze the phylogeny of the medically important and taxonomically unresolved viper genus Echis using four mitochondrial gene fragments. The results show that the populations of the genus fall into four main clades: the Echis carinatus, E. coloratus, E. ocellatus and E. pyramidum groups. The E. pyramidum and E. coloratus groups are sister taxa but the interrelationships of this clade and the E. ocellatus and E. carinatus groups are unresolved. The initial divergence of the genus appears to coincide with the collision between Afro-Arabia and Eurasia, and that between the E. coloratus and E. pyramidum clades appears to be associated with the opening of the Red Sea. Later land connections between Africa and Arabia may have contributed to shaping the distribution of the E. pyramidum complex. The present distribution of E. carinatus may be the result of range expansion from southern India. Taxonomically, our results provide molecular evidence for the validity of Echis omanensis, E. khosatzkii, E. borkini and E. jogeri, for the presence of unsuspected genetic diversity within the E. pyramidum complex in eastern Africa, and for the conspecificity of E. carinatus and E. multisquamatus. The status of E. leucogaster remains to be confirmed.
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coevolution of diet and prey specific venom activity supports the role of selection in snake venom evolution
Proceedings of The Royal Society B: Biological Sciences, 2009Co-Authors: Axel Barlow, Robert A. Harrison, Catharine E Pook, Wolfgang WusterAbstract:The processes that drive the evolution of snake venom variability, particularly the role of diet, have been a topic of intense recent research interest. Here, we test whether extensive variation in venom composition in the medically important viper genus Echis is associated with shifts in diet. Examination of stomach and hindgut contents revealed extreme variation between the major clades of Echis in the proportion of arthropod prey consumed. The toxicity (median lethal dose, LD50) of representative Echis venoms to a natural scorpion prey species was found to be strongly associated with the degree of arthropod feeding. Mapping the results onto a novel Echis phylogeny generated from nuclear and mitochondrial sequence data revealed two independent instances of coevolution of venom toxicity and diet. Unlike venom LD50, the speed with which venoms incapacitated and killed scorpions was not associated with the degree of arthropod feeding. The prey-specific venom toxicity of arthropod-feeding Echis may thus be adaptive primarily by reducing venom expenditure. Overall, our results provide strong evidence that variation in snake venom composition results from adaptive evolution driven by natural selection for different diets, and underscores the need for a multi-faceted, integrative approach to the study of the causes of venom evolution.
