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(Presenters in Bold)
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Neuroinflammation and oxidative stress induced by Kv channel-blocker: Neuroprotective effect of Coenzyme Q10
Nesrine Ahras-Sifi1, Amina Ladjel-Mendil1, Marie-France Martin-Eauclaire2 and Fatima Laraba-Djebari1
1 USTHB, Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, BP32, El Alia, Bab Ezzouar, 16111 Algiers, Algeria
2 CRN2M UMR 7286, CNRS, Aix Marseille Universite´, 13344 Marseille Cedex 15, France
Kaliotoxin (KTx) is a neurotoxin purified from the venom of Androctonus australis hector scorpion, it blocks specifically the voltage-dependent potassium channel (Kv). These channels contribute to the regulation of the potential of action in neurons, where they are involved in the repolarization phase. Dysfunction of Kv channels has been associated to seizures. Neuroinflammation, oxidative stress and mitochondrial dysfunction play an important role in the pathophysiology of seizures. The present study has been designed to investigate the role of coenzyme Q10 an essential cofactor of the electron transport chain in mitochondrial against disorders caused by KTx…
Involvement of cytokines in neuroinflammatory disorders induced by Kaliotoxin
Zahida Taibi-Djennah1, Nesrine Ahras-Sifi1, Marie-France Martin-Eauclaire2, Fatima Laraba-Djebari1
1 Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, University of Sciences and Technology HouariBoumdiene, BP 32 El-Alia, Bab Ezzouar, 16111 Algiers, Algeria
2 CRN2M UMR 7286, CNRS, Aix Marseille Universite´, 13344 Marseille Cedex 15, France
Scorpion venom is a rich source of various peptides that are useful for biological research. Kaliotoxin (KTx), a neurotoxin isolated from Androctonusaustralis hector venom, acts on voltage-gated potassium (Kv) channels. The binding of KTx to its targets in the brain, is able to alter neuronal excitability leading to neurological disorders, accompanied by inflammatory response activation and immunological mediator release. The pro-inflammatory cytokines are known to induce local and systemic responses. In the present study, we investigated the contribution of IL-6 and TNF-α in the modulation of neuroinflammatory…
Serological profiling of novel anti-neurotoxic and anti-haemotoxic antivenoms designed to treat snakebite in sub-Saharan Africa
Jaffer Alsolaiss and Robert Harrison
The Alistair Reid Venom Research Unit, Parasitology Department, Liverpool School of Tropical Medicine, Liverpool, Merseyside L3 5QA, United Kingdom
Background: Snakebite is a Neglected Tropical Disease. The most economically-productive and educationally-vulnerable 15-30-year-old Africans suffer disproportionally high rates of snakebite-induced mortality (32,000 deaths) and disability. The very limited availability of polyspecifically effective and affordable antivenom is the most important contributor to this disease burden. This study is part of a MRC-funded project to use a novel ‘antivenomic’ approach to develop a single antivenom for sub-Saharan Africa. The first phase of the project is serological profiling of IgG from sheep immunised with venoms exerting the greatest neurotoxic or hemotoxic effects…
Preliminary study of Vipera ursinii macrops venom composition and biological activity
Maja Lang Balija1, Marija Brgles1, Monika Tunjic1, Adrijana Leonardi2, Tihana Kurtovic1, Igor Križaj2, Beata Halassy1
1 Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, 10000 Zagreb, Republic of Croatia
2 Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia
Meadow vipers (Vipera ursinii) form a group of five subspecies, but their distribution area is highly fragmented and covers Europe, Western and Central Asia. Karst viper, Vipera ursinii macrops (Vum) inhabits high mountain grasslands in Croatia, Bosnia and Herzegovina, Serbia, Macedonia, Montenegro and northern Albania. In Croatia it is a highly threatened viper species that appears only in five isolated localities. Scientific literature on V. ursinii deals only with its morphology, ecology and distribution range due to the species’ conservation problems, while its venom composition and properties have not been investigated…
The DoubleBARR Restraining Frame for handling venomous snakes
Diana Barr1,2, Owen Paiva1,2, Benjamin Bande2, David J Williams1,2
1 Australian Venom Research Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, VIC, 3010. Australia
2 Charles Campbell Toxinology Centre, School of Medicine and Health Sciences, University of Papua New Guinea, Port Moresby, NCD, 121. Papua New Guinea
The production of snake venoms is fundamental to the manufacture of snake antivenom immunoglobulins, since these complex mixtures of proteins and peptides provide the immunogens necessary for driving the production of IgG antibodies by host animals. Venoms are also used for basic research and for biodiscovery applications by many institutions and companies around the world. Conventional snake handling techniques often expose handlers to unnecessary risk of accidental envenoming. In order to collect venom samples, snakes must be physically restrained and either encouraged to bite so that venom is released into a suitable collection vessel, or manipulated…
Role of the non-toxic fraction (F1) purified from Androctonus australis hector venom on early hepatocarcinoma induced by Fumonisin B1
Nadjia BEKKARI and Fatima LARABA DJEBARI
USTHB, Faculty of Biological Sciences, Laboratory of cellular and Molecular Biology, 16111, BP32, El Alia, Bab Ezzouar, Algiers, Algeria
Scorpion venoms are mixture of bioactive components which are known by their high toxicity, but their use as tools in therapeutic is in progress. This study was undertaken to investigate the ability of the purified non toxic fraction of Androctonus australis hector (Aah) venom to restore carcinogenic effect of fumonisin B1 on the liver. An evaluation of oxidative marker levels (pro-oxidative and anti-oxidative mediators), enzymatic activities, DNA quantification and tissue analysis were assessed. Obtained results showed that carcinogenesis initiated by fumonisin B1 was characterized by biomarker disturbance (unbalance of oxidative status and DNA alteration)…
The Presynaptic Activity of Tityus bahiensis (brown scorpion) venom
Rita CO Collaço1; Valquíria AC Dorce2; Edward G Rowan3; Edson Antunes1
1 Department of Pharmacology, State University of Campinas. Campinas, SP, Brazil
2 Laboratory of Pharmacology, Butantan Institute. São Paulo, SP, Brazil
3 Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
Scorpion envenomation produces local and systemic effects predominantly increasing neurotransmitter release by venom-containing neurotoxic peptides, which exhibit high selectivity for ion channels. Despite Tityus bahiensis (T. bahiensis) being responsible for the majority of scorpion stings in Brazil, its venom remains poorly studied especially on the somatic nervous system. Here, we investigated the neurotoxicity of T. bahiensis venom using myographic and electrophysiological approaches. In mouse phrenic nerve-diaphragm preparations (PND), T. bahiensis venom at a low concentration…
Inflammatory mediators in victims of Botrhops snakebites in Brazilian Amazon Region
Iran Mendonça da Silva1,2, Jacqueline A. G. Sachett1,2, Eliane Campos-Alves1,2, Sâmella S. Oliveira1,2, Vanderson S. Sampaio1,2,3,Antônio Magela Tavares2, Marcus V. G. Lacerda1,2,5, Luiz C. L. Ferreira1,2,4, Allyson Guimarães da Costa2, Wuelton Marcelo Monteiro1,2
1 Escola Superior de Saúde, Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil
2 Departamento de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil
3 Núcleo de Sistemas de Informação, Fundação de Vigilância em Saúde do Amazonas, Manaus, Brazil
4 Faculdade de Medicina, Universidade Federal do Amazonas, Manaus, Brazil
5 Instituto de Pesquisas Leônidas & Maria Deane, FIOCRUZ, Manaus, Brazil
A prospective cohort study was conducted to evaluate inflammation in Botrhops atrox snakebite in Dr Vieira Dourado Tropical Medicine Foundation – Manaus – Amazonas State (FMT-HVD), for the period from August 2014 to February 2016. It was performed laboratorial analysis like bloodstream venom race, blood clotting and inflammation markers like erythrocyte sedimentation rate, C-reactive protein, creatine kinase, dehydrogenase, alanine aminotransferase, aspartate aminotransferase and several serum cytokines at the times after snakebite (0-12 hours, 12-24 hours, 24-48 hours, 48-72 hours and after 7 days)…
Efficacy of Amoxicillin Clavulanate in Preventing Secondary Infection – Bothrops Snakebites in Brazilian Amazon: Randomized Controlled Clinical Trial
Jacqueline A. G. Sachett1,2, Iran Mendonça da Silva1,2, Eliane Campos-Alves1,2, Sâmella S. Oliveira1,2, Vanderson S. Sampaio1,2,3, Fábio Francesconi do Vale1,4, Gustavo Romero1,5, Marcelo Cordeiro dos Santos1,2, Hedylamar Oliveira Marques6, Mônica Colombini7, Ana Maria Moura da Silva7, Fan Wen Hui7, Marcus V. G. Lacerda1,2,8, Wuelton M. Monteiro1,2,#, Luiz C. L. Ferreira1,2,4
1 Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
2 Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, Brazil
3 Núcleo de Sistemas de Informação, Fundação de Vigilância em Saúde do Amazonas, Manaus, Brazil
4 Faculdade de Medicina, Universidade Federal do Amazonas, Manaus, Brazil
5 Faculdade de Medicina. Universidade de Brasília, Brasília, Brazil
6 Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas
7 Instituto Butantan, São Paulo, Brazil
8 Instituto de Pesquisas Leônidas & Maria Deane, FIOCRUZ, Manaus, Brazil
The aim of this work was to estimate the efficacy of amoxicillin clavulanate for reducing the secondary infection incidence in patients bitten by Bothrops snakes and identify risk factors for secondary infections from snakebites in the Western Brazilian Amazon. This was an open-label, two-arm individually randomized superiority trial to prevention secondary infection from Bothrops snakebites. The antibiotic chosen for this clinical trial was oral tablet amoxicillin clavulanate per seven days. A total of 345 patients were assessed for eligibility in the study period. From this total, 187 accomplished the inclusion criteria and were randomized, with 93 in the interventional group…
Discovery and engineering of recombinant antibodies targeting Naja nigricollis toxins
Andrea Martos Esteban, Mogens Kilstrup, Andreas Hougaard Laustsen
DTU Bioengineering, Technical University of Denmark, Søltofts Plads, building 221, Kongens Lyngby 2800, Denmark
Snakebite envenomation is a major public health issue and it is one of the top 20 most neglected tropical diseases defined by the World Health Organization. Snakebite envenomation is an environmental and occupational health hazard that not only causes more than 100,000 deaths per year, but also economic catastrophe for victims and families living in impoverished communities of Africa, Central and South America, and Asia. The only effective treatment against the snakebite envenomation is the use of heterologous serum obtained after hyper-immunization of horses with selected snake venoms. Due to the production method, existing antivenoms are immunogenic, often causing adverse reactions in patients upon administration…
Purification and pharmacological characterization of b-neurotoxins from Micrurus lemniscatus lemniscatus (South American coral-snake) venom
Rafael S Floriano1,3, Patrícia C Panunto1, Nelson J da Silva Jr.2, Edward G Rowan3, Stephen Hyslop1
1 Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, 13083-887, Campinas, SP, Brazil
2 Department of Biology, Pontifical Catholic University (PUC), Rua 232, 128, 74605-140, Goiânia, GO, Brazil
3 Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Cathedral Street, 161, G4 0RE, Glasgow, UK
Micrurus venoms are known for their neurotoxicity, which is mediated by a-neurotoxins (three-finger toxins–3FTx) and b-neurotoxins (phospholipases–PLA2). Here, we have purified and characterized the activity of two toxins from M. l. lemniscatus venom. The crude venom was fractioned in HPLC-RP system using a column C-18 and the fractions subjected to enzymatic assay to determine those with PLA2 activity. The neuromuscular activity of the fractions-PLA2 was investigated through measurement of miniature end-plate potentials (MEPPs) in mouse phrenic nerve-diaphragm (PND) preparation followed by measurement of perineural currents in mouse triangularis sterni nerve-muscle (TSn-m)…
Hemodynamic and vascular responses to Micrurus lemniscatus lemniscatus (South American coral-snake) venom
Rafael S Floriano1,4, Julio A Rojas-Moscoso1, Lourdes Dias1, Thalita Rocha2, Nelson J da Silva Jr.3, Edward G Rowan4, Stephen Hyslop1
1 Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, 13083-887, Campinas, SP, Brazil.
2 Multidisciplinary Research Laboratory, São Francisco University (USF), Av. São Francisco de Assis, 218, 12916-900, Bragança Paulista, SP, Brazil
3 Department of Biology, Pontifical Catholic University (PUC), Rua 232, 128, 74605-140, Goiânia, GO, Brazil
4 Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Cathedral Street, 161, G4 0RE, Glasgow, UK
Micrurus lemniscatus lemniscatus is a coral snake found in the northern region of Brazil and occasionally causes envenomation in humans. In this study, we have investigated the hemodynamic and vascular responses to M. l. lemniscatus venom in anesthetized male Wistar rats and in rat isolated thoracic aorta preparation. Samples of heart and lungs from anesthetized rats were dissected for histological analysis. Venom caused immediate hypotension that was maximal within the first minute [AP: 98±3 vs. 63±4 mmHg (35±1.5% decrease) and 103±4 vs. 56±4 mmHg (46±3.2% decrease) for 0.1 and 0.3 mg/kg, respectively (n=4, p<0.05); both doses were lethal after 20-40 min….
Design of scFab-based chimeric antibodies against snake venom metalloproteinase from Bothrops asper
Rasmus U. W. Friis1,2, Søren H. Dam1,2, Aleksander M. Haack1,2, Malte B. Hallgren1,2, Andrea M. Esteban1, Mikael R. Andersen1, Mogens Kilstrup1, Andreas H. Laustsen1
1 Department of Biotechnology and Biomedicine, Technical University of Denmark
2 Department of Bio and Health Informatics, Technical University of Denmark
Snakebite envenoming is one of the world’s most neglected tropical diseases, responsible for the death of 125,000 people each year. The only current treatment is antivenom based on antiserum derived from the blood of immunised mammals. This antiserum is costly to produce and carries a high risk of causing adverse effects in human recipients because of its heterologous origin. Furthermore, due to poor tissue permeability, antivenom against locally acting snake toxins targeting peripheral tissue is less effective. Consequently, an impending…
The Cytotoxic Effect of Slow Loris (Nycticebus) Venom on Human Epidermal Carcinoma Cells
Matthew Gardiner1, Priya Samuel2, Carol M Trim3 and Danielle McCullough3, K.A.I. Nekaris1
1 Oxford Brookes University, Faculty of Humanities and Social Sciences, Oxford, UK
2 Oxford Brookes University, Faculty of Health and Life Sciences, Oxford, UK
3 Section of Life Sciences, School of Human and Life Sciences, Canterbury Christ Church University, Canterbury, CT1 1QU, UK
Within the Kingdom Mammalia, venom evolution is rare, occurring in only six orders. Arguably the most cryptic, and academically neglected venom occurs within primates among slow lorises (Nycticebus spp.). Venoms comprise novel biological compounds with a potential plethora of proteins and peptides available for utilisation in bio-medical research. We collected samples of slow loris saliva from eight captive-bred pygmy slow lorises (N. pygmaeus) at Paignton Zoo and Shaldon Wildlife Trust UK, given voluntarily as slow lorises chewed on Salimetrics children’s swabs…
Preliminary study of the cytotoxicity of king cobra (Ophiophagus hannah) L-amino acid oxidase (Laao) in cell lines of acute lymphoblastic leukaemia
Suzanne McPherson1, Victoria McCormack1, Ken Mills1, Jeremy W Hamilton2
1 Blood cancer research group, Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast, UK
2 Haematology Department, Ulster Hospital, Belfast, UK
King Cobra (LAAO) has a wide range of potential therapeutic applications and has previously demonstrated cytotoxicity in cell line models of breast, lung and prostate cancer. Acute Lymphoblastic Leukaemia (ALL) is a haematological malignancy in which abnormal lymphoblasts replace the bone marrow. Untreated this disease is rapidly fatal and despite progress with chemotherapy, immunotherapy and molecularly targeted drugs 5yr survival remains poor at approximately 40% in adults. Further advances in treatment are necessary. The amino acid asparagine is essential for lymphoblast metabolism and L asparaginase is an integral component of treatment…
An improved technique for the assessment of venom-induced haemorrhage in mice
Timothy P Jenkins1, Andrés Sánchez2, Álvaro Segura2, Mariángela Vargas2, María Herrera2,3, Jose María Gutiérrez2, Guillermo León2
1 Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
2 Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica
3 Sección de Química Analítica, Escuela de Química, Universidad de Costa Rica, San José, Costa Rica.
Snakebite envenomings pose a significant risk to public health globally, causing mortality and morbidity to hundreds of thousands of victims each year. Currently, the only specific treatment for systemic envenoming is the intravenous administration of antivenom. However, the efficacy of antivenoms to neutralize toxicity has to be demonstrated through preclinical testing before being used clinically. The assessment focuses on the antivenoms’ efficacy in neutralising venom-induced lethality, but also includes other key toxic activities such as myotoxicity, dermonecrosis and haemorrhage. Particularly haemorrhage is of importance, since it is one of the most common clinical…
Comparative Transcriptomic Analysis of Venom Gland Tissues from Spitting and Non-spitting Cobras
Taline Kazandjian
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA , UK
Cobras are highly venomous elapid snakes that inhabit Asia and Africa and cause thousands of deaths each year. Some cobras have specialised fangs that allow them to eject venom as a spray into the eyes of an aggressor, causing immediate pain, opthalmia and, occasionally, blindness. Spitting cobras have therefore evolved a novel, defensive use of their venom that is not observed in other venomous snakes. The aim of this study was to assess whether the venom composition of spitting cobras has changed in response to the evolution of this defensive adaptation. Using the venom glands from 16 species of cobra, transcriptomic libraries were generated, sequenced, annotated and the…
A new generation of antivenoms to treat Dendroaspis polylepis bites
Cecilie Knudsen1, Aneesh Karatt-Vellat2, Mikael R. Andersen1, Robert Harrison3, Nicholas Casewell3, Mogens Kilstrup1, John McCafferty2, Andreas H. Laustsen1
1 Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark
2 IONTAS, Iconix Park, London Road, Pampisford, Cambridge CB223EG, United Kingdom
3 Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
Snakebite is one of the major health concerns in rural, tropical parts of the world. Each year, 5 million bites occur, leading to 2.5 million cases of envenoming, 125,000 deaths, and 400,000 amputations. Survivors, who are often agricultural workers and children, frequently lose their limbs and thus their ability to work, underlining the socio-economic issues related to snakebite. The current treatment consists of animal-derived antibodies, which are expensive to produce and which due to their heterologous origin are likely to induce immunologic side-effects, such as serum-sickness and anaphylactic shock. The goal of the research presented here is to develop a safer, cheaper, and more efficacious snakebite antivenom based…
Development of recombinant human antivenom against forest cobra toxins
Line Ledsgaard1; Mia Øhenschlæger1; Aneesh Karatt-Vellatt2, Mikael R Andersen1; Robert Harrison3; Nicholas Casewell3; John McCafferty2; Andreas H Laustsen1
1 Department of Biotechnology and Biomedicine, Technical University of Denmark
2 IONTAS Ltd. Cambridge, United Kingdom
3 Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine
Every year around 5 million people are bitten by venomous snakes, resulting in 125.000 deaths and 400.000 amputations. The only effective treatment against snake envenoming is antivenom, which has been based on animal-derived antibodies for more than 100 years. Due to the heterologous nature of the antivenom, treatment against snakebite envenoming can inflict severe side effects, such as serum sickness and anaphylaxis, which in some cases may lead to death. Due to the severity of snakebite combined with the lack of research in novel antivenom, the World Health Organization (WHO) characterizes snakebite envenoming as one of the world’s most neglected tropical diseases…
Effects of two Phospholipases A2 (Asp-49 and Lys 49) isolated from Bothrops pauloensis venom on isolated kidney of rat
Aline D Marinho1; Antonio R C Jorge1; Adriano J M C Filho1; Francisco A N Junior1; Pedro L lopes1; Venucia B M Pereira1; Roberto C P L Junior1; Danielle M Gaspar1; Marcos H Toyama2; Helena S A Monteiro1
1 Department of Physiology and Pharmacology, Federal University of Ceara (UFC), Fortaleza-CE 60430-275, Brazil
2 Sao Vicente Unit, Paulista Coastal Campus, Sao Paulo State University (UNESP), São Vicente-SP 11330-900, Brazil
Acute renal failure (ARF) wich is one of the most serious complications of Bothrops snakebites, is one of the main causes of death and consequences for victims. However, its pathogenesis remains unclear. Considering that isolated toxins are relevant tools for understanding the actions of the whole venom, we studied properties of phospholipases A2 (Asp-49 and Lys-49) isolated from Bothrops pauloensis (from State of São Paulo, Southeast region of Brazil),on isolated perfused kidney of rat. The control group perfused with modified Krebs–Henseleit solution alone. Asp-49 increased the perfusion pressure (PP), renal vascular resistance (RVR)…
Discovery of human IgG antibodies against key venom toxins from the Central American coral snake (Micrurus nigrocinctus)
Erick Bermúdez Méndez1, Julián Fernández2, Bruno Lomonte2, José María Gutiérrez2, Andreas H Laustsen1
1 Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
2 Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica
Snakebite envenoming remains a major public health issue in Latin America and other rural tropical regions of the world, causing mortality and morbidity to hundreds of thousands. Particularly in Central America, the species Micrurus nigrocinctus is the most abundant and clinically relevant coral snake from the Elapidae family. The venom of M. nigrocinctus is predominantly composed of phospholipases A2 (PLA2s) and three-finger toxins (3FTxs), constituting 48% and 38% of the venom proteins, respectively. Snakebites from this species predominantly induce neurotoxic effects, although myotoxicity has been shown in animal models and may occur in humans…
Venom in furs: pelage as an aposematic signal in slow lorises (Primates, Nycticebus)
Anne-Isola Nekaris, Matthew Gardiner, Ariana Weldon, Stephanie A Poindexter
Nocturnal Primate Research Group, Oxford Brookes University, Oxford, UK
The evolutionary function of colouration in mammals includes concealment, communication, and interspecific signalling including the use of aposematism as a warning signal. Several mammals use aposematism to warn predators of their dangerous odour or unpalatability. The slow loris is the only venomous mammal that has a coat pattern with distinctive dark and light markings, suggesting a potential aposematic role. To help understand if slow lorises use conspicuous aposematism to advertise their venom to potential predators or slow loris competitors, we measured colouration in 54 known wild individuals (37 adults, 17 juveniles) from photographs taken in the field under similar lighting conditions…
In vivo neutralization potential of monoclonal human IgGs against elapid neurotoxins
Urska Pus1, Andreas H. Laustsen1, Aneesh Karatt-Vellatt2, Daniel T. Griffiths2, Saioa Oscoz4, Mikael R. Andersen1, Robert Harrison3, Nicholas Casewell3, Bruno Lomonte4, John McCafferty2, José María Gutiérrez4
1 Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
2 IONTAS, Iconix Park, London Road, Pampisford, Cambridge CB223EG, United Kingdom
3 Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
4 Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica
The Black mamba (Dendroaspis polylepis) and the monocled cobra (Naja kaouthia) are two notorious venomous snakes belonging to the elapid family, causing a considerable share of the severe envenomings occurring in sub-Saharan Africa and Southeast Asia, respectively. In this study, monoclonal fully human IgGs were discovered by a combined toxicovenomics and phage display selection approach and assessed for their ability to neutralize medically relevant toxins from these snakes in vivo. Upon expression in mammalian Expi-293 cells, the monoclonal human IgGs were assessed using two different routes of administration in CD-1 mice. First, IgGs and their target neurotoxins (a-neurotoxins and dendrotoxins)…
Identification of Cobra Venom Actives as Potential Novel Pancreatic Cancer Therapeutics
Emily L Knight1, Carol M Trim1 and Steven A Trim2
1 Section of Life Sciences, School of Human and Life Sciences, Canterbury Christ Church University, Canterbury, CT1 1QU, UK
2 Venomtech Ltd, Discovery Park House, Discovery Park, Sandwich, Kent, CT13 9ND, UK
Pancreatic cancer is an aggressive form of cancer which has a particularly poor prognosis. Currently only 3% of patients survive more than five years and just 1% of patients survive for more than ten years after diagnosis. This highlights the urgent need for development of novel treatments for pancreatic cancer and the importance of early diagnosis. Animal venom contains a complex mixture of proteins, peptides, enzymes and small molecules. In addition to their negative effects on human health, components from venoms have been utilised as treatments for conditions such as hypertension, angina and even cancer…
A compact and effective procedure for antivenom downstream processing
Tihana Kurtovic, Maja Lang Balija, Monika Tunjic, Marija Brgles, Beata Halassy
University of Zagreb, Center for Research and Knowledge Transfer in Biotechnology, Rockefellerova 10, 10000 Zagreb, Croatia
Antivenoms obtained from hyperimmune animal plasma, mostly equine or ovine, are the only specific therapeutics effective for rapidly counteracting post-snakebite pathophysiological manifestations. There are various well established refinement processing strategies that have been implemented into commercial scale antivenom production. However, optimisation of manufacturing process yielding safe, effective and available immunotherapeutics is still of great concern. Here, we report simple, feasible and economically viable fractionation protocol for preparation of V. a. ammodytes-specific antivenom. Hyperimmune equine plasma pool was fractionated in only few simple…
