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Ruslan I Alshekhadat - One of the best experts on this subject based on the ideXlab platform.

  • 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
    Co-Authors: Sarai Quesadabernat, Susana Mesen, Denis O Mustafin, Yulia A Fomina, Mauren Villalta, Alvaro Segura, Mariangela Vargas, Andrés Sánchez, Yania Rodríguez, Ruslan I Alshekhadat
    Abstract:

    Abstract 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.

  • 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
    Co-Authors: Sarai Quesadabernat, Susana Mesen, Denis O Mustafin, Yulia A Fomina, Mauren Villalta, Alvaro Segura, Mariangela Vargas, Andrés Sánchez, Yania Rodríguez, Ruslan I Alshekhadat
    Abstract:

    Abstract 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.

Sarai Quesadabernat - One of the best experts on this subject based on the ideXlab platform.

  • 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
    Co-Authors: Sarai Quesadabernat, Susana Mesen, Denis O Mustafin, Yulia A Fomina, Mauren Villalta, Alvaro Segura, Mariangela Vargas, Andrés Sánchez, Yania Rodríguez, Ruslan I Alshekhadat
    Abstract:

    Abstract 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.

  • 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
    Co-Authors: Sarai Quesadabernat, Susana Mesen, Denis O Mustafin, Yulia A Fomina, Mauren Villalta, Alvaro Segura, Mariangela Vargas, Andrés Sánchez, Yania Rodríguez, Ruslan I Alshekhadat
    Abstract:

    Abstract 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.

Tamas Malina - One of the best experts on this subject based on the ideXlab platform.

  • extending knowledge of the clinical picture of balkan adder Vipera berus bosniensis envenoming the first photographically documented neurotoxic case from south western hungary
    Toxicon, 2018
    Co-Authors: Csaba Varga, Tamas Malina, Viktoria Alfoldi, Gergely Bilics, Ferenc Nagy, Tibor Olah
    Abstract:

    Abstract We report a severe envenoming associated with minimal local symptoms following a Balkan adder (Vipera berus bosniensis) bite in South-Western Hungary. A 63-year-old male with a history of hypertension and sinus bradycardia (45/min) was bitten by a sub-adult specimen of V. b. bosniensis in Somogy County on 04 May 2017. The patient was transported to and treated at the Emergency Department of “Moritz Kaposi” General Hospital, Kaposvar. Locally only pain and minimal swelling with a small haematoma developed on the bitten finger. The abdominal muscles were very tender and guarding was detected upon palpation on the way to hospital. The patient, who had taken his telmisartan (80 mg) tablet in that morning, complained of nausea and dizziness during the first medical examination. The systemic signs included fluctuations in blood pressure (115/85–165/105 mmHg), ECG changes (transient horizontal ST depression in V5-6, and sinus tachycardia (90/min)), severe diarrhoea and vomiting (in 7 episodes). Descending neuromuscular paralysis appeared in the next morning, including complete bilateral ptosis with external ophthalmoplegia, and binocular diplopia. Single-fiber electromyography confirmed the neuromuscular block in the frontalis muscle innervated by the facial nerve. Intense dizziness with uncoordinated movement emerged on the 3rd day. The laboratory findings were mild, including anaemia, hypokalaemia, elevated glutamic-pyruvic transaminase and C-reactive protein levels. The absolute neutrophil count remained almost completely normal. Supportive care and monovalent antivenom (Viper Venom Antitoxin®, Biomed, Warsaw) were applied. The patient was discharged from hospital on the 4th day, although recovery was not complete until 9 days after the bite. This is the first photographically-documented case of neurotoxic envenoming from the South-Western Hungarian distribution range of V. b. bosniensis.

  • individual variability of venom from the european adder Vipera berus berus from one locality in eastern hungary
    Toxicon, 2017
    Co-Authors: Tamas Malina, Laszlo Krecsak, David A Warrell, Alexander Westerstrom, Gabor Szemannagy, Gyoengyi Gyemant, Marta Mhamvas, E G Rowan, Alan L Harvey, Zoltan Rusznak
    Abstract:

    We have revealed intra-population variability among venom samples from several individual European adders (Vipera berus berus) within a defined population in Eastern Hungary. Individual differences in venom pattern were noticed, both gender-specific and age-related, by one-dimensional electrophoresis. Gelatin zymography demonstrated that these individual venoms have different degradation profiles indicating varying protease activity in the specimens from adders of different ages and genders. Some specimens shared a conserved region of substrate degradation, while others had lower or extremely low protease activity. Phospholipase A2 activity of venoms was similar but not identical. Interspecimen diversity of the venom phospholipase A2-spectra (based on the components' molecular masses) was detected by MALDI-TOF MS. The lethal toxicity of venoms (LD50) also showed differences among individual snakes. Extracted venom samples had varying neuromuscular paralysing effect on chick biventer cervicis nerve-muscle preparations. The paralysing effect of venom was lost when calcium in the physiological salt solution was replaced by strontium; indicating that the block of twitch responses to nerve stimulation is associated with the activity of a phospholipase-dependent neurotoxin. In contrast to the studied V. b. berus venoms from different geographical regions so far, this is the first V. b. berus population discovered to have predominantly neurotoxic neuromuscular activity. The relevance of varying venom yields is also discussed. This study demonstrates that individual venom variation among V. b. berus living in particular area of Eastern Hungary might contribute to a wider range of clinical manifestations of V. b. berus envenoming than elsewhere in Europe.

  • first clinical experiences about the neurotoxic envenomings inflicted by lowland populations of the balkan adder Vipera berus bosniensis
    Neurotoxicology, 2011
    Co-Authors: Tamas Malina, Laszlo Krecsak, Dusan Jelic, Tomislav Maretic, Tamas Toth, Marijan Sisko, Nenad Pandak
    Abstract:

    The first overall clinical description of envenomings by the lowland populations of the Balkan adder (Vipera berus bosniensis) is provided by this study. Fifty-four incidents have been collected retrospectively from the south-western Hungarian and the northern Croatian distribution area of the taxon. There were five (9%) asymptomatic, 24 (44%) mild, 12 (22%) moderate, 12 (22%) severe, and one fatal (2%) case according to the Poisoning Severity Score. The single death is a 60-year-old Hungarian case that was caused by V.b. bosniensis. Average hospitalisation was 2.75 days. The most common systemic symptoms were gastrointestinal disorders, ECG changes, persisting hypotension and neurological disorders. The initial phase of neurotoxic manifestations was always expressed in cranial nerve disturbances: ptosis, external ophthalmoplegia, diplopia, reduced focusing capability and blurred vision. Neuromuscular paralysis progressed to dyspnoea and lower limb paralysis in the most severe cases. Unusual symptoms were fluctuating arterial hypertension, drowsiness, and hypokalaemia. Laboratory results reveal leucocytosis, while deviation in the other laboratory values is not common. Envenomings by V.b. bosniensis significantly differ from those by the European adder (Vipera berus berus) in lower manifestation rate of extensive oedema, anaemia, CNS depression, and haematuria but the development of neuromuscular paralysis is high (20%). Their bites rather resulted in mild and moderate local symptoms in envenomed patients than those inflicted by the nominate form. This study presents the evidence of the frequent neurotoxic manifestations in Balkan adder-bitten patients for the first time, which strongly suggests that the venom of the lowland populations of V.b. bosniensis has neurotoxic activity.

  • neurotoxicity and hypertension following european adder Vipera berus berus bites in hungary case report and review
    QJM: An International Journal of Medicine, 2008
    Co-Authors: Tamas Malina, Laszlo Krecsak, David A Warrell
    Abstract:

    In Europe, the common adder ( Vipera berus ) is extensively distributed and causes more bites than any other species in the genus Vipera.1 In Hungary, there are two subspecies; the nominate form ( V. b. berus ) in the East and Northeast and the Bosnian adder ( V. b. bosniensis ) in the Southwest (Figures 1 and 2).2 Figure 1. Common adders ( Vipera berus ) from Hungary: ( a and b ) V. b. berus , female specimens from the population where our patient was bitten (Vamosatya, Szabolcs–Szatmar–Bereg County, E Hungary) (Photographs Tamas Malina). ( c ) V. b. bosniensis female from Darvaspuszta, Somogy County, SW Hungary (Photographs Zoltan Korsos). Envenomings by V. berus result in characteristic systemic symptoms including early ‘anaphylactic’ features such as tachycardia, dizziness, hypotension, shock and gastrointestinal symptoms, coagulopathy and neutrophil leucocytosis.1,3,4 These symptoms resemble those caused by V. aspis , reflecting the similarities in the composition of their venoms.5 Systemic neurotoxicity has been described in patients envenomed by certain populations of some subspecies of V. aspis and V. ammodytes in Europe.6 It has been attributed to pre-synaptic (ammodytoxins) or post-synaptic neurotoxic phospholipases A2 (PLA2) in their venoms.6 However, neurotoxicity is a most unusual and unexpected clinical feature of V. berus envenoming. We describe here a case from eastern Hungary with other interesting features and review the scanty and somewhat obscure literature on this phenomenon. ### Case report A previously healthy 27-year-old man was bitten by an adult female V. berus 70–72 cm in total length on 23 April 2007 in Szabolcs–Szatmar–Bereg County in eastern Hungary (Figure 2). The snake was captured alive and expertly identified. The victim reported no previous snakebites. Two fangs impaled the left thumb, causing burning pain that became throbbing in quality. The bitten finger swelled immediately and a small haematoma formed at the …

Thomas Madsen - One of the best experts on this subject based on the ideXlab platform.

  • genetic rescue restores long term viability of an isolated population of adders Vipera berus
    Current Biology, 2020
    Co-Authors: Thomas Madsen, Jon Loman, Lewis Anderberg, Hakan Anderberg, Arthur Georges, Beata Ujvari
    Abstract:

    Climate change is regarded as a major threat to global biodiversity [1]. However, another key driver of declines in biodiversity during the last century has been, and still is, the devastating impact of anthropogenic habitat destruction [2]. Human degradation of natural habitats has resulted in large, formerly homogeneous areas becoming exceedingly isolated and fragmented, resulting in reduced genetic diversity and a concomitant increased vulnerability to pathogens [3] and increased risk of inbreeding [4]. In order to restore genetic diversity in small isolated or fragmented populations, genetic rescue - that is, an intervention in which unrelated individuals are brought into a population, leading to introduction of novel alleles - has been shown to reduce the deleterious effects of inbreeding [4,5].

  • novel genes continue to enhance population growth in adders Vipera berus
    Biological Conservation, 2004
    Co-Authors: Thomas Madsen, Beata Ujvari, Mats Olsson
    Abstract:

    In 1999, we published a report on how an introduction of 20 males into a severely inbred and isolated population of adders (Vipera berus) halted its decline towards extinction, induced a profound change in population genetic variability, resulted in a dramatic increase in offspring viability and thus in a rapid increase in numbers. Since the publication of our paper we have received numerous inquiries as to whether we have continued to monitor this population, as this is the case we herein present population demographic data gathered between 1981 and 2003. The population has continued to increase in numbers and in 2003, we collected 39 adult male adders, more than at any time over the 23-year study. Our continued work, hence, lends strong support to the importance of novel genes in enhancing the viability of inbred populations and supports the importance of preserving genetic variability in order to maintain viable wild populations.

  • promiscuity in sand lizards lacerta agilis and adder snakes Vipera berus causes and consequences
    Journal of Heredity, 2001
    Co-Authors: Mats Olsson, Thomas Madsen
    Abstract:

    We review postcopulatory phenomena in the Swedish sand lizard (Lacerta agilis) and adder (Vipera berus), and in particular, links between female promiscuity, determinants of paternity, and offspring viability. In both species, females mate multiply and exhibit a positive relationship between the number of partners and offspring viability. We conclude that this relationship is most likely the result of variable genetic compatibility between mates arising from postcopulatory phenomena, predominantly assortative fertilization with respect to parental genotypes, However, males who were more successful at mate acquisition were also more successful in situations of sperm competition, suggesting a possible link between male (diploid and haploid) genetic quality per se and probability of fertilization, Neither the number of partners nor the number of matings influenced the risk of infertility in sand lizards, suggesting that selection for reduced risk of infertility is not a sufficient explanation for maintaining female promiscuity in this population. Finally, we conclude that the relatively low genetic variability exhibited by our study populations may have facilitated detection of genetic benefits compared to more outbred ones. However, recent work derived from outbred populations in other tars suggest a greater generality of the principles we discuss than previously may have been appreciated.

  • population size and genetic diversity in sand lizards lacerta agilis and adders Vipera berus
    Biological Conservation, 2000
    Co-Authors: Thomas Madsen, Bo Stille, Richard Shine, Mats Olsson, Hakan Wittzell, Annica Gullberg, Stefan Andersson, Hakan Tegelstrom
    Abstract:

    Because low genetic diversity may threaten the viability of isolated populations, conservation biologists have devoted much effort to quantify genetic variation. Two techniques routinely used involve levels of mini- and microsatellite polymorphism, with the assumption that levels of variation at these parts of the genome will be reflected in levels of variation at other loci. Our data challenge this assumption. We studied six populations of sand lizards (Lacerta agilis) and five populations of adders (Vipera berus), differing considerably in size and degree of isolation. They, therefore, offer an opportunity to examine how population parameters affect genetic variation at different parts of the genome. Relative population size (based on degree of isolation and number of animals) was not correlated with either minisatellite variability or microsatellite heterozygosity. However, our measures of genetic diversity at the Mhc class I loci of both sand lizards and adders revealed a significant correlation between relative population size and Mhc polymorphism: non-isolated/larger populations exhibited higher genetic diversity than did isolated/small populations. Consequently, only the Mhc-based estimates of genetic diversity yielded results in agreement with population genetic theory. (C) 2000 Elsevier Science Ltd. All rights reserved.

  • population size and genetic diversity in sand lizards lacerta agilis and adders Vipera berus
    Biological Conservation, 2000
    Co-Authors: Thomas Madsen, Bo Stille, Richard Shine, Mats Olsson, Hakan Wittzell, Annica Gullberg, Stefan Andersson, Hakan Tegelstrom
    Abstract:

    Because low genetic diversity may threaten the viability of isolated populations, conservation biologists have devoted much effort to quantify genetic variation. Two techniques routinely used involve levels of mini- and microsatellite polymorphism, with the assumption that levels of variation at these parts of the genome will be reflected in levels of variation at other loci. Our data challenge this assumption. We studied six populations of sand lizards (Lacerta agilis) and five populations of adders (Vipera berus), differing considerably in size and degree of isolation. They, therefore, offer an opportunity to examine how population parameters affect genetic variation at different parts of the genome. Relative population size (based on degree of isolation and number of animals) was not correlated with either minisatellite variability or microsatellite heterozygosity. However, our measures of genetic diversity at the Mhc class I loci of both sand lizards and adders revealed a significant correlation between relative population size and Mhc polymorphism: non-isolated/larger populations exhibited higher genetic diversity than did isolated/small populations. Consequently, only the Mhc-based estimates of genetic diversity yielded results in agreement with population genetic theory. (C) 2000 Elsevier Science Ltd. All rights reserved.

Alvaro Segura - One of the best experts on this subject based on the ideXlab platform.

  • 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
    Co-Authors: Sarai Quesadabernat, Susana Mesen, Denis O Mustafin, Yulia A Fomina, Mauren Villalta, Alvaro Segura, Mariangela Vargas, Andrés Sánchez, Yania Rodríguez, Ruslan I Alshekhadat
    Abstract:

    Abstract 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.

  • 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
    Co-Authors: Sarai Quesadabernat, Susana Mesen, Denis O Mustafin, Yulia A Fomina, Mauren Villalta, Alvaro Segura, Mariangela Vargas, Andrés Sánchez, Yania Rodríguez, Ruslan I Alshekhadat
    Abstract:

    Abstract 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.

  • Vipera berus berus Venom from Russia: Venomics, Bioactivities and Preclinical Assessment of Microgen Antivenom
    MDPI AG, 2019
    Co-Authors: Ruslan I. Al-shekhadat, Alvaro Segura, Ksenia S. Lopushanskaya, José María Gutiérrez, Juan J. Calvete, Davinia Pla
    Abstract:

    The common European adder, Vipera berus berus, is a medically relevant species, which is widely distributed in Russia and thus, is responsible for most snakebite accidents in Russia. We have investigated the toxic and enzymatic activities and have determined the proteomic composition of its venom. Phospholipases A2 (PLA2, 25.3% of the venom proteome), serine proteinases (SVSP, 16.2%), metalloproteinases (SVMP, 17.2%), vasoactive peptides (bradykinin-potentiating peptides (BPPs), 9.5% and C-type natriuretic peptides (C-NAP, 7.8%), cysteine-rich secretory protein (CRISP, 8%) and L-amino acid oxidase (LAO, 7.3%) represent the major toxin classes found in V. b. berus (Russia) venom. This study was also designed to assess the in vivo and in vitro preclinical efficacy of the Russian Microgen antivenom in neutralizing the main effects of V. b. berus venom. The results show that this antivenom is capable of neutralizing the lethal, hemorrhagic and PLA2 activities. Third-generation antivenomics was applied to quantify the toxin-recognition landscape and the maximal binding capacity of the antivenom for each component of the venom. The antivenomics analysis revealed that 6.24% of the anti-V. b. berus F(ab’)2 molecules fraction are toxin-binding antibodies, 60% of which represent clinically relevant antivenom molecules