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Keywords = Vipera berus

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12 pages, 239 KB  
Article
Clinical Efficacy and Pharmacokinetics of Antivenom Viperfav® in Vipera ammodytes ammodytes Envenomation
by Tihana Kurtović, Mojca Dobaja Borak, Damjan Grenc, Adrijana Leonardi, Igor Križaj, Boris Lukšić, Beata Halassy and Miran Brvar
Pharmaceutics 2025, 17(11), 1431; https://doi.org/10.3390/pharmaceutics17111431 - 5 Nov 2025
Viewed by 651
Abstract
Background: In Europe, Vipera ammodytes ammodytes (Vaa, nose-horned viper) is considered the most venomous of the European vipers. The antivenom Viperfav®, composed of polyvalent equine F(ab′)2 fragments, is effective against Vipera aspis, Vipera berus and Vaa. [...] Read more.
Background: In Europe, Vipera ammodytes ammodytes (Vaa, nose-horned viper) is considered the most venomous of the European vipers. The antivenom Viperfav®, composed of polyvalent equine F(ab′)2 fragments, is effective against Vipera aspis, Vipera berus and Vaa. Objectives: This study aimed to evaluate the clinical efficacy and pharmacokinetics of Viperfav in Vaa envenomations. Methods: Patients presenting with Vaa snakebite and treated with intravenous Viperfav were included. Clinical manifestations and laboratory findings were assessed on admission to the Emergency Department, prior to antivenom therapy, and monitored throughout hospitalization. Blood samples were collected on arrival and at defined intervals after Viperfav administration. Venom and antivenom concentrations in serum were determined by ELISA and subjected to pharmacokinetic analysis. Results: Twenty-one patients bitten by Vaa and classified with a severity score of 2b on the modified Audebert clinical severity scale received a single intravenous dose of Viperfav within 4 h of the bite. Viperfav attenuated the progression of local symptoms and prevented the development of new systemic manifestations. The serum concentrations of F(ab′)2 fragments reached 196 µg/mL, far exceeding the venom concentration at admission (35 ng/mL). The prolonged elimination half-life of Viperfav (49 h) corresponded with the absence of recurrent symptoms after a single dose. Bradycardia or hypotension occurred in 10% of patients; no cases of anaphylaxis or serum sickness were observed. Conclusions: A single intravenous dose of Viperfav demonstrated clinical efficacy and a favourable pharmacokinetic profile in Vaa envenomed patients when administered within hours of the bite. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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20 pages, 5554 KB  
Data Descriptor
Diversity of Helminths of Reptiles (Serpentes and Lacertilia) in the Middle Volga Region (European Russia)
by Alexander A. Kirillov, Nadezhda Yu. Kirillova, Alexander B. Ruchin, Alexander I. Fayzulin and Sergei V. Shchenkov
Diversity 2025, 17(6), 380; https://doi.org/10.3390/d17060380 - 28 May 2025
Cited by 2 | Viewed by 1473
Abstract
This paper presents an analysis of helminth diversity in reptiles in eight provinces of the Middle Volga region (European Russia) based on the dataset recently published in the GBIF as the Darwin Core Archive. The dataset contains up-to-date information on the occurrence of [...] Read more.
This paper presents an analysis of helminth diversity in reptiles in eight provinces of the Middle Volga region (European Russia) based on the dataset recently published in the GBIF as the Darwin Core Archive. The dataset contains up-to-date information on the occurrence of parasitic worms in lizards and snakes and summarizes the records obtained during long-term helminthological studies conducted in 1996–2024. It includes 8576 helminth occurrence records in nine reptile species inhabiting the Middle Volga region. All helminth occurrence records are georeferenced. In total, we present data on 45 parasitic worm species, including 4 species of cestodes, 21 species of trematodes, 16 species of nematodes, and 4 species of acanthocephalans. The richest helminth fauna was found in Natrix natrix (26 species), Lacerta agilis (21), Natrix tessellata (16), and Vipera berus (15). Less diverse is the helminth fauna in Anguis colchica (8 species), Zootoca vivipara (7), Vipera renardi (6), Coronella austriaca (5), and Eremias arguta (3). The diversity of helminths in reptiles of the Middle Volga region does not reach its maximum compared to other European countries. Most helminth species found in lizards and snakes of the studied region belong to the Palearctic faunal complex (25 species). Eight species of parasites have a Holarctic distribution. Seven helminth species parasitize reptiles only in Europe. Five species of parasites are cosmopolitan. Of the 45 species of helminths found in reptiles, 3 species have medical and veterinary significance as causative agents of dangerous helminthiasis. Data on the diversity and distribution of parasitic worms in reptiles of the Middle Volga region remain incomplete, so further observations may provide new occurrence records of helminths and expand the knowledge about their hosts. Full article
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24 pages, 7201 KB  
Review
A Guide to the Clinical Management of Vipera Snakebite in Italy
by Matteo Riccardo Di Nicola, Marta Crevani, Ignazio Avella, Anna Cerullo, Jean-Lou C. M. Dorne, Giovanni Paolino and Caterina Zattera
Toxins 2024, 16(6), 255; https://doi.org/10.3390/toxins16060255 - 31 May 2024
Cited by 14 | Viewed by 9488
Abstract
The genus Vipera encompasses most species of medically significant venomous snakes of Europe, with Italy harbouring four of them. Envenomation by European vipers can result in severe consequences, but underreporting and the absence of standardised clinical protocols hinder effective snakebite management. This study [...] Read more.
The genus Vipera encompasses most species of medically significant venomous snakes of Europe, with Italy harbouring four of them. Envenomation by European vipers can result in severe consequences, but underreporting and the absence of standardised clinical protocols hinder effective snakebite management. This study provides an updated, detailed set of guidelines for the management and treatment of Vipera snakebite tailored for Italian clinicians. It includes taxonomic keys for snake identification, insights into viper venom composition, and recommendations for clinical management. Emphasis is placed on quick and reliable identification of medically relevant snake species, along with appropriate first aid measures. Criteria for antivenom administration are outlined, as well as indications on managing potential side effects. While the protocol is specific to Italy, its methodology can potentially be adapted for other European countries, depending on local resources. The promotion of comprehensive data collection and collaboration among Poison Control Centres is advocated to optimise envenomation management protocols and improve the reporting of epidemiological data concerning snakebite at the country level. Full article
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7 pages, 1282 KB  
Case Report
Cold Finger: Raynaud Phenomenon Following Snakebite Envenoming by Nikolsky’s Viper (Vipera berus nikolskii)
by Oleksandr Zinenko, Daniela M. Durkin, Rebecca W. Carter, Brandi Ritter and Matthew R. Lewin
Toxins 2023, 15(10), 598; https://doi.org/10.3390/toxins15100598 - 4 Oct 2023
Cited by 3 | Viewed by 2541
Abstract
A field biologist was bitten by a female Nikolsky’s viper (Vipera berus nikolskii) in Kharkiv Oblast, Ukraine. Two months later, the patient began to experience cold-induced vasospasm of the affected digit diagnosed as acquired Raynaud phenomenon. The patient had more than [...] Read more.
A field biologist was bitten by a female Nikolsky’s viper (Vipera berus nikolskii) in Kharkiv Oblast, Ukraine. Two months later, the patient began to experience cold-induced vasospasm of the affected digit diagnosed as acquired Raynaud phenomenon. The patient had more than 30 occurrences during the single winter following the bite, but the signs and symptoms of Raynaud phenomenon disappeared with the end of winter. This report describes the case and puts it into context with the literature on the topic of toxin-induced peripheral vasospastic disorders and their potential importance in snakebite envenoming. Full article
(This article belongs to the Section Animal Venoms)
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7 pages, 4280 KB  
Proceeding Paper
Snakebites in Domestic Animals
by Andreia Garcês, Catarina Pereira, Maria Inês Santiago, Justina Prada, Filipe Silva and Isabel Pires
Biol. Life Sci. Forum 2023, 24(1), 4; https://doi.org/10.3390/IECT2023-14798 - 17 Jul 2023
Cited by 1 | Viewed by 3679
Abstract
In Portugal, there are four venomous species, the horned viper (Vipera latastei), seoane (Vipera seoanei), rat snake (Malpolon monspessulanus), and the hooded snake (Macroprotodon brevis ibericus), and in the UK, there is one: the common [...] Read more.
In Portugal, there are four venomous species, the horned viper (Vipera latastei), seoane (Vipera seoanei), rat snake (Malpolon monspessulanus), and the hooded snake (Macroprotodon brevis ibericus), and in the UK, there is one: the common European adder (Vipera berus). Snake venom is a complex mixture of toxins whose composition varies depending on the family, genera, species, and even subspecies. In Europe, particularly Portugal, there are no published data on the frequency of these types of incidents, but it is estimated to be high, mainly in dogs. Thus, to characterize the injuries caused by the bite of venomous snakes in domestic animals, the authors describe cases in dogs, cats, and goats with a suspected snakebite. Animals presented wounds compatible with snakebites, with two points 1 to 1.8 cm apart that could be noted on the head or limbs. The main clinical signs observed included pain, oedema, and necrosis. From the animals that died, a post-mortem examination revealed subcutaneous and muscular necrosis and hemorrhages of surrounding tissues, including muscles and organic hemorrhages. The severity of envenomation depends on the quantity of inoculated venom; the species, age, size, and previous state of health of the bitten animal; the bite location; and post-bite excitability. With this study, the authors hope to help improve the knowledge regarding snakebites in Europe. Full article
(This article belongs to the Proceedings of The 2nd International Electronic Conference on Toxins)
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16 pages, 3393 KB  
Article
Cytogenetic Analysis of the Bimodal Karyotype of the Common European Adder, Vipera berus (Viperidae)
by Victor Spangenberg, Ilya Redekop, Sergey A. Simanovsky and Oxana Kolomiets
Animals 2022, 12(24), 3563; https://doi.org/10.3390/ani12243563 - 16 Dec 2022
Cited by 8 | Viewed by 4387
Abstract
Vipera berus is the species with the largest range of snakes on Earth and one of the largest among reptiles in general. It is also the only snake species found in the Arctic Circle. Vipera berus is the most involved species of the [...] Read more.
Vipera berus is the species with the largest range of snakes on Earth and one of the largest among reptiles in general. It is also the only snake species found in the Arctic Circle. Vipera berus is the most involved species of the genus Vipera in the process of interspecific hybridization in nature. The taxonomy of the genus Vipera is based on molecular markers and morphology and requires clarification using SC-karyotyping. This work is a detailed comparative study of the somatic and meiotic karyotypes of V. berus, with special attention to DNA and protein markers associated with synaptonemal complexes. The karyotype of V. berus is a remarkable example of a bimodal karyotype containing both 16 large macrochromosomes and 20 microchromosomes. We traced the stages of the asynchronous assembly of both types of bivalents. The number of crossing-over sites per pachytene nucleus, the localization of the nucleolar organizer, and the unique heterochromatin block on the autosomal bivalent 6—an important marker—were determined. Our results show that the average number of crossing-over sites per pachytene nucleus is 49.5, and the number of MLH1 sites per bivalent 1 reached 11, which is comparable to several species of agamas. Full article
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8 pages, 781 KB  
Case Report
Neurotoxicity and Other Clinical Manifestations of a Common European Adder (Vipera berus) Bite in Romania
by Gabriela Viorela Nițescu, Coriolan Emil Ulmeanu, Maria-Dorina Crăciun, Alina Maria Ciucă, Alexandru Ulici, Ioan Ghira and Davide Lonati
Toxins 2022, 14(7), 500; https://doi.org/10.3390/toxins14070500 - 18 Jul 2022
Cited by 6 | Viewed by 4197
Abstract
Most cases of envenomation by common European vipers (Vipera berus) have not been reported to have neurotoxic manifestations. However, these manifestations have been demonstrated in some cases of envenomation by subspecies of V. berus, found in the Carpathian Basin region [...] Read more.
Most cases of envenomation by common European vipers (Vipera berus) have not been reported to have neurotoxic manifestations. However, these manifestations have been demonstrated in some cases of envenomation by subspecies of V. berus, found in the Carpathian Basin region of south-eastern Europe. Here, we report the case of a 5-year-old girl from the south of Romania who presented symptoms of neurotoxicity, as well as other systemic and local symptoms, after being bitten by an adder of the V. berus subspecies. Treatment consisted of monovalent antivenom, a corticosteroid, and prophylactic enoxaparin. Neurotoxic manifestations of envenomation as well as other local and systemic symptoms improved within 5 days of treatment. The presented case shows that venom from V. berus subspecies found in the Carpathian Basin can have neurotoxic effects. This case also confirmed the efficacy of monospecific antivenom treatment in bringing about rapid and complete remission, following envenomation. Full article
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15 pages, 1837 KB  
Article
Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab’)2 Fragments in Vipera ammodytes-Envenomed Patients
by Tihana Kurtović, Svjetlana Karabuva, Damjan Grenc, Mojca Dobaja Borak, Igor Križaj, Boris Lukšić, Beata Halassy and Miran Brvar
Toxins 2021, 13(4), 279; https://doi.org/10.3390/toxins13040279 - 14 Apr 2021
Cited by 10 | Viewed by 4153
Abstract
Vipera ammodytes (V. ammodytes) is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous Vipera berus venom-specific (paraspecific) Fab fragments (ViperaTAb) and intramuscular V. ammodytes venom-specific F(ab’)2 fragments [...] Read more.
Vipera ammodytes (V. ammodytes) is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous Vipera berus venom-specific (paraspecific) Fab fragments (ViperaTAb) and intramuscular V. ammodytes venom-specific F(ab’)2 fragments (European viper venom antiserum, also called “Zagreb” antivenom) in V.ammodytes-envenomed patients. This was a prospective study of V.ammodytes-envenomed patients that were treated intravenously with ViperaTAb or intramuscularly with European viper venom antiserum that was feasible only due to the unique situation of an antivenom shortage. The highest venom concentration, survival, length of hospital stay and adverse reactions did not differ between the groups. Patients treated with intravenous Fab fragments were sicker, with significantly more rhabdomyolysis and neurotoxicity. The kinetics of Fab fragments after one or more intravenous applications matched better with the venom concentration in the early phase of envenomation compared to F(ab’)2 fragments that were given intramuscularly only on admission. F(ab’)2 fragments given intramuscularly had 25-fold longer apparent total body clearance and 14-fold longer elimination half-time compared to Fab fragments given intravenously (2 weeks vs. 24 h, respectively). In V.ammodytes-envenomed patients, the intramuscular use of specific F(ab’)2 fragments resulted in a slow rise of antivenom serum concentration that demanded their early administration but without the need for additional doses for complete resolution of all clinical signs of envenomation. Intravenous use of paraspecific Fab fragments resulted in the immediate rise of antivenom serum concentration that enabled their use according to the clinical progress, but multiple doses might be needed for efficient therapy of thrombocytopenia due to venom recurrence, while the progression of rhabdomyolysis and neurotoxic effects of the venom could not be prevented. Full article
(This article belongs to the Special Issue Toxinology and Pharmacology of Snake Venoms)
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11 pages, 1374 KB  
Article
Comparison of Preclinical Properties of Several Available Antivenoms in the Search for Effective Treatment of Vipera ammodytes and Vipera berus Envenoming
by Tihana Kurtović, Maja Lang Balija, Miran Brvar, Mojca Dobaja Borak, Sanja Mateljak Lukačević and Beata Halassy
Toxins 2021, 13(3), 211; https://doi.org/10.3390/toxins13030211 - 13 Mar 2021
Cited by 12 | Viewed by 3809
Abstract
Snakebites are a relatively rare medical emergency in Europe. In more than half of the annual cases caused by Vipera ammodytes, Vipera berus, and Vipera aspis, immunotherapy with animal-derived antivenom is indicated. Among eight products recently identified as available against [...] Read more.
Snakebites are a relatively rare medical emergency in Europe. In more than half of the annual cases caused by Vipera ammodytes, Vipera berus, and Vipera aspis, immunotherapy with animal-derived antivenom is indicated. Among eight products recently identified as available against European medically relevant species, only Zagreb antivenom, Viperfav, and ViperaTAb have been used almost exclusively for decades. Zagreb antivenom comprises V. ammodytes-specific F(ab′)2 fragments. Viperfav is a polyspecific preparation based on F(ab′)2 fragments against V. aspis, V. berus, and V. ammodytes venoms. ViperaTAb contains Fab fragments against the venom of V. berus. In 2014 the production of Zagreb antivenom was discontinued. Additionally, in the period of 2017 to 2018 a shortage of Viperfav occurred. Due to a lack of the product indicated for the treatment of V. ammodytes bites, other antivenoms were implemented into clinical practice without comparative assessment of their eligibility. The aim of our work was to identify a high-quality antivenom that might ensure the successful treatment of V. ammodytes and V. berus bites at the preclinical level. Differentiation between bites from these two species is difficult and unreliable in clinical practice, so the availability of a unique antivenom applicable in the treatment of envenoming caused by both species would be the most advantageous for Southeastern Europe. Zagreb antivenom, Viperfav, and ViperaTAb, as well as Viper venom antitoxin for V. berus envenoming and the in-development Inoserp Europe, which was designed to treat envenoming caused by all medically important European snakes, were comparatively tested for the first time. Emphasis was placed on their physicochemical properties, primarily purity and aggregate content, as well as their in vivo protective efficacies. As Zagreb antivenom is no longer available on the European market, Viperfav is the highest-quality product currently available and the only antivenom whose neutralisation potency against V. ammodytes and V. berus venoms was above regulatory requirements. Full article
(This article belongs to the Section Animal Venoms)
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7 pages, 429 KB  
Article
PLA2 Inhibitor Varespladib as an Alternative to the Antivenom Treatment for Bites from Nikolsky’s Viper Vipera berus nikolskii
by Oleksandr Zinenko, Igor Tovstukha and Yevgen Korniyenko
Toxins 2020, 12(6), 356; https://doi.org/10.3390/toxins12060356 - 29 May 2020
Cited by 33 | Viewed by 6333
Abstract
Although envenoming by a small East European species of viper is rarely severe, and only exceptionally fatal, lack of specific antivenom stocks in a few areas within this region and possible severe side effects of antivenom application leave most bites to be treated [...] Read more.
Although envenoming by a small East European species of viper is rarely severe, and only exceptionally fatal, lack of specific antivenom stocks in a few areas within this region and possible severe side effects of antivenom application leave most bites to be treated only with antihistamines and supportive therapy. Varespladib is an effective inhibitor of snake phospholipase, and, as such, it could be considered as first-line therapy. The Nikolsky’s viper venom contains an extremely high concentration of phospholipase A2 (PLA2), responsible for the toxic effects of the venom, as well as minor amounts of other toxins. If Varespladib can successfully inhibit PLA2 activity, the Nikolsky’s viper could be one of the first venomous snakes having an antitoxin-specific treatment regimen. To assess that, Varespladib was administered alone subcutaneously to adult male CD-1 mice (8 mg/kg) and compared to mice exposed to Vipera berus nikolskii crude venom (8 mg/kg = 10 LD50) or a combination of Varespladib and the same amount of the venom. Experimental animals were monitored for the presence of envenoming symptoms and mortality for 48 h after injection. Eighty percent of mice receiving both Varespladib and venom survived, while 100% of the control group receiving venom alone died within 4 h. Experimental results are consistent with Varespladib acting as an effective antitoxin in the mouse model against Nikolsky’s viper venom. Further studies are needed under experimental conditions that more closely resemble natural envenoming (i.e., delayed administration). Full article
(This article belongs to the Section Animal Venoms)
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11 pages, 1395 KB  
Article
Preclinical Assessment of a New Polyvalent Antivenom (Inoserp Europe) against Several Species of the Subfamily Viperinae
by Alejandro García-Arredondo, Michel Martínez, Arlene Calderón, Asunción Saldívar and Raúl Soria
Toxins 2019, 11(3), 149; https://doi.org/10.3390/toxins11030149 - 5 Mar 2019
Cited by 21 | Viewed by 5099
Abstract
The European continent is inhabited by medically important venomous Viperinae snakes. Vipera ammodytes, Vipera berus, and Vipera aspis cause the greatest public health problems in Europe, but there are other equally significant snakes in specific regions of the continent. Immunotherapy is [...] Read more.
The European continent is inhabited by medically important venomous Viperinae snakes. Vipera ammodytes, Vipera berus, and Vipera aspis cause the greatest public health problems in Europe, but there are other equally significant snakes in specific regions of the continent. Immunotherapy is indicated for patients with systemic envenoming, of which there are approximately 4000 annual cases in Europe, and was suggested as an indication for young children and pregnant women, even if they do not have systemic symptoms. In the present study, the safety and venom-neutralizing efficacy of Inoserp Europe—a new F(ab’)2 polyvalent antivenom, designed to treat envenoming by snakes in the Eurasian region—were evaluated. In accordance with World Health Organization recommendations, several quality control parameters were applied to evaluate the safety of this antivenom. The venom-neutralizing efficacy of the antivenom was evaluated in mice and the results showed it had appropriate neutralizing potency against the venoms of several species of Vipera, Montivipera, and Macrovipera. Paraspecificity of the antivenom was demonstrated as well, since it neutralized venoms of species not included in the immunization schemes and contains satisfactory levels of total proteins and F(ab’)2 fragment concentration. Therefore, this new polyvalent antivenom could be effective in the treatment of snake envenoming in Europe, including Western Russia and Turkey. Full article
(This article belongs to the Section Animal Venoms)
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14 pages, 1233 KB  
Article
Vipera berus berus Venom from Russia: Venomics, Bioactivities and Preclinical Assessment of Microgen Antivenom
by Ruslan I. Al-Shekhadat, Ksenia S. Lopushanskaya, Álvaro Segura, José María Gutiérrez, Juan J. Calvete and Davinia Pla
Toxins 2019, 11(2), 90; https://doi.org/10.3390/toxins11020090 - 1 Feb 2019
Cited by 33 | Viewed by 9818
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Discovery of Antibodies and Novel Antivenoms against Envenoming)
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13 pages, 1567 KB  
Article
Proteome and Peptidome of Vipera berus berus Venom
by Aleksandra Bocian, Małgorzata Urbanik, Konrad Hus, Andrzej Łyskowski, Vladimír Petrilla, Zuzana Andrejčáková, Monika Petrillová and Jaroslav Legath
Molecules 2016, 21(10), 1398; https://doi.org/10.3390/molecules21101398 - 19 Oct 2016
Cited by 36 | Viewed by 7759
Abstract
Snake venom is a rich source of peptides and proteins with a wide range of actions. Many of the venom components are currently being tested for their usefulness in the treatment of many diseases ranging from neurological and cardiovascular to cancer. It is [...] Read more.
Snake venom is a rich source of peptides and proteins with a wide range of actions. Many of the venom components are currently being tested for their usefulness in the treatment of many diseases ranging from neurological and cardiovascular to cancer. It is also important to constantly search for new proteins and peptides with properties not yet described. The venom of Vipera berus berus has hemolytic, proteolytic and cytotoxic properties, but its exact composition and the factors responsible for these properties are not known. Therefore, an attempt was made to identify proteins and peptides derived from this species venom by using high resolution two-dimensional electrophoresis and MALDI ToF/ToF mass spectrometry. A total of 11 protein classes have been identified mainly proteases but also l-amino acid oxidases, C-type lectin like proteins, cysteine-rich venom proteins and phospholipases A2 and 4 peptides of molecular weight less than 1500 Da. Most of the identified proteins are responsible for the highly hemotoxic properties of the venom. Presence of venom phospholipases A2 and l-amino acid oxidases cause moderate neuro-, myo- and cytotoxicity. All successfully identified peptides belong to the bradykinin-potentiating peptides family. The mass spectrometry data are available via ProteomeXchange with identifier PXD004958. Full article
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16 pages, 2418 KB  
Communication
Varespladib (LY315920) Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation
by Matthew Lewin, Stephen Samuel, Janie Merkel and Philip Bickler
Toxins 2016, 8(9), 248; https://doi.org/10.3390/toxins8090248 - 25 Aug 2016
Cited by 189 | Viewed by 16362
Abstract
Snakebite remains a neglected medical problem of the developing world with up to 125,000 deaths each year despite more than a century of calls to improve snakebite prevention and care. An estimated 75% of fatalities from snakebite occur outside the hospital setting. Because [...] Read more.
Snakebite remains a neglected medical problem of the developing world with up to 125,000 deaths each year despite more than a century of calls to improve snakebite prevention and care. An estimated 75% of fatalities from snakebite occur outside the hospital setting. Because phospholipase A2 (PLA2) activity is an important component of venom toxicity, we sought candidate PLA2 inhibitors by directly testing drugs. Surprisingly, varespladib and its orally bioavailable prodrug, methyl-varespladib showed high-level secretory PLA2 (sPLA2) inhibition at nanomolar and picomolar concentrations against 28 medically important snake venoms from six continents. In vivo proof-of-concept studies with varespladib had striking survival benefit against lethal doses of Micrurus fulvius and Vipera berus venom, and suppressed venom-induced sPLA2 activity in rats challenged with 100% lethal doses of M. fulvius venom. Rapid development and deployment of a broad-spectrum PLA2 inhibitor alone or in combination with other small molecule inhibitors of snake toxins (e.g., metalloproteases) could fill the critical therapeutic gap spanning pre-referral and hospital setting. Lower barriers for clinical testing of safety tested, repurposed small molecule therapeutics are a potentially economical and effective path forward to fill the pre-referral gap in the setting of snakebite. Full article
(This article belongs to the Section Animal Venoms)
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7 pages, 576 KB  
Case Report
A Single Dose of ViperfavTM May Be Inadequate for Vipera ammodytes Snake Bite: A Case Report and Pharmacokinetic Evaluation
by Tihana Kurtović, Miran Brvar, Damjan Grenc, Maja Lang Balija, Igor Križaj and Beata Halassy
Toxins 2016, 8(8), 244; https://doi.org/10.3390/toxins8080244 - 19 Aug 2016
Cited by 14 | Viewed by 6638
Abstract
ViperfavTM is a commercial F(ab’)2 antivenom prepared against European vipers venom. It is safe and effective for treating envenomation caused by Vipera aspis and Vipera berus. Therapeutic efficacy for treating Vipera ammodytes ammodytes (V. a. ammodytes) envenoming has not been [...] Read more.
ViperfavTM is a commercial F(ab’)2 antivenom prepared against European vipers venom. It is safe and effective for treating envenomation caused by Vipera aspis and Vipera berus. Therapeutic efficacy for treating Vipera ammodytes ammodytes (V. a. ammodytes) envenoming has not been yet described, although protective efficacy has been demonstrated in preclinical studies. We report on a 32-year-old man bitten by V. a. ammodytes who was treated with Viperfav™. Viperfav™ promptly reduced local extension and improved systemic pathological signs, but 24 h after the incident a recurrence of thrombocytopenia occurred despite a favorable pharmacokinetic profile with systemic clearance (1.64 (mL·h−1)·kg−1) and elimination half-life (97 h) among the highest ever reported. The recommended dose of Viperfav™ for V. aspis and V. berus bites may be inadequate for serious V. a. ammodytes envenomations. Following V. a. ammodytes bite, serial blood counts and coagulation profiles should be performed to help guide Viperfav™ treatment, along with supplemental administration as indicated. Full article
(This article belongs to the Section Animal Venoms)
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