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Article ; Online: Development of a membrane-disruption assay using phospholipid vesicles as a proxy for the detection of cellular membrane degradation.

Bittenbinder, Mátyás A / Wachtel, Eric / Pereira, Daniel Da Costa / Slagboom, Julien / Casewell, Nicholas R / Jennings, Paul / Kool, Jeroen / Vonk, Freek J

Toxicon: X

2024 Volume 22, Page(s) 100197

Abstract: Snakebite envenoming is a global health issue that affects millions of people worldwide, and that causes morbidity rates surpassing 450,000 individuals annually. Patients suffering from snakebite morbidities may experience permanent disabilities such as ... ...

Abstract	Snakebite envenoming is a global health issue that affects millions of people worldwide, and that causes morbidity rates surpassing 450,000 individuals annually. Patients suffering from snakebite morbidities may experience permanent disabilities such as pain, blindness and amputations. The (local) tissue damage that causes these life-long morbidities is the result of cell- and tissue-damaging toxins present in the venoms. These compounds belong to a variety of toxin classes and may affect cells in various ways, for example, by affecting the cell membrane. In this study, we have developed a high-throughput
Language	English
Publishing date	2024-04-07
Publishing country	England
Document type	Journal Article
ISSN	2590-1710
ISSN (online)	2590-1710
DOI	10.1016/j.toxcx.2024.100197
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Studying Venom Toxin Variation Using Accurate Masses from Liquid Chromatography-Mass Spectrometry Coupled with Bioinformatic Tools.

Alonso, Luis L / van Thiel, Jory / Slagboom, Julien / Dunstan, Nathan / Modahl, Cassandra M / Jackson, Timothy N W / Samanipour, Saer / Kool, Jeroen

Toxins

2024 Volume 16, Issue 4

Abstract: This study provides a new methodology for the rapid analysis of numerous venom samples in an automated fashion. Here, we use LC-MS (Liquid Chromatography-Mass Spectrometry) for venom separation and toxin analysis at the accurate mass level combined with ... ...

Abstract	This study provides a new methodology for the rapid analysis of numerous venom samples in an automated fashion. Here, we use LC-MS (Liquid Chromatography-Mass Spectrometry) for venom separation and toxin analysis at the accurate mass level combined with new in-house written bioinformatic scripts to obtain high-throughput results. This analytical methodology was validated using 31 venoms from all members of a monophyletic clade of Australian elapids: brown snakes (
MeSH term(s)	Animals ; Computational Biology ; Elapid Venoms/chemistry ; Elapid Venoms/analysis ; Elapidae ; Liquid Chromatography-Mass Spectrometry
Chemical Substances	Elapid Venoms
Language	English
Publishing date	2024-04-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins16040181
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Article ; Online: Acetylcholine-Binding Protein Affinity Profiling of Neurotoxins in Snake Venoms with Parallel Toxin Identification.

Palermo, Giulia / Schouten, Wietse M / Alonso, Luis Lago / Ulens, Chris / Kool, Jeroen / Slagboom, Julien

International journal of molecular sciences

2023 Volume 24, Issue 23

Abstract: Snakebite is considered a concerning issue and a neglected tropical disease. Three-finger toxins (3FTxs) in snake venoms primarily cause neurotoxic effects since they have high affinity for nicotinic acetylcholine receptors (nAChRs). Their small ... ...

Abstract	Snakebite is considered a concerning issue and a neglected tropical disease. Three-finger toxins (3FTxs) in snake venoms primarily cause neurotoxic effects since they have high affinity for nicotinic acetylcholine receptors (nAChRs). Their small molecular size makes 3FTxs weakly immunogenic and therefore not appropriately targeted by current antivenoms. This study aims at presenting and applying an analytical method for investigating the therapeutic potential of the acetylcholine-binding protein (AChBP), an efficient nAChR mimic that can capture 3FTxs, for alternative treatment of elapid snakebites. In this analytical methodology, snake venom toxins were separated and characterised using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) and high-throughput venomics. By subsequent nanofractionation analytics, binding profiling of toxins to the AChBP was achieved with a post-column plate reader-based fluorescence-enhancement ligand displacement bioassay. The integrated method was established and applied to profiling venoms of six elapid snakes (
MeSH term(s)	Animals ; Neurotoxins/toxicity ; Elapid Venoms/chemistry ; Acetylcholine ; Three Finger Toxins ; Snake Venoms ; Toxins, Biological ; Elapidae/metabolism ; Snake Bites ; Receptors, Nicotinic
Chemical Substances	Neurotoxins ; Elapid Venoms ; Acetylcholine (N9YNS0M02X) ; Three Finger Toxins ; Snake Venoms ; Toxins, Biological ; Receptors, Nicotinic
Language	English
Publishing date	2023-11-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242316769
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Article ; Online: Metabolome-Based Classification of Snake Venoms by Bioinformatic Tools.

Alonso, Luis L / Slagboom, Julien / Casewell, Nicholas R / Samanipour, Saer / Kool, Jeroen

Toxins

2023 Volume 15, Issue 2

Abstract: Snakebite is considered a neglected tropical disease, and it is one of the most intricate ones. The variability found in snake venom is what makes it immensely complex to study. These variations are present both in the big and the small molecules found ... ...

Abstract	Snakebite is considered a neglected tropical disease, and it is one of the most intricate ones. The variability found in snake venom is what makes it immensely complex to study. These variations are present both in the big and the small molecules found in snake venom. This study focused on examining the variability found in the venom's small molecules (i.e., mass range of 100-1000 Da) between two main families of venomous snakes-Elapidae and Viperidae-managing to create a model able to classify unknown samples by means of specific features, which can be extracted from their LC-MS data and output in a comprehensive list. The developed model also allowed further insight into the composition of snake venom by highlighting the most relevant metabolites of each group by clustering similarly composed venoms. The model was created by means of support vector machines and used 20 features, which were merged into 10 principal components. All samples from the first and second validation data subsets were correctly classified. Biological hypotheses relevant to the variation regarding the metabolites that were identified are also given.
MeSH term(s)	Animals ; Humans ; Snake Venoms ; Elapidae/metabolism ; Viperidae/metabolism ; Snake Bites ; Mass Spectrometry ; Elapid Venoms/metabolism
Chemical Substances	Snake Venoms ; Elapid Venoms
Language	English
Publishing date	2023-02-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins15020161
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Article ; Online: Acetylcholine-Binding Protein Affinity Profiling of Neurotoxins in Snake Venoms with Parallel Toxin Identification

Giulia Palermo / Wietse M. Schouten / Luis Lago Alonso / Chris Ulens / Jeroen Kool / Julien Slagboom

International Journal of Molecular Sciences, Vol 24, Iss 23, p

2023 Volume 16769

Abstract	Snakebite is considered a concerning issue and a neglected tropical disease. Three-finger toxins (3FTxs) in snake venoms primarily cause neurotoxic effects since they have high affinity for nicotinic acetylcholine receptors (nAChRs). Their small molecular size makes 3FTxs weakly immunogenic and therefore not appropriately targeted by current antivenoms. This study aims at presenting and applying an analytical method for investigating the therapeutic potential of the acetylcholine-binding protein (AChBP), an efficient nAChR mimic that can capture 3FTxs, for alternative treatment of elapid snakebites. In this analytical methodology, snake venom toxins were separated and characterised using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) and high-throughput venomics. By subsequent nanofractionation analytics, binding profiling of toxins to the AChBP was achieved with a post-column plate reader-based fluorescence-enhancement ligand displacement bioassay. The integrated method was established and applied to profiling venoms of six elapid snakes ( Naja mossambica , Ophiophagus hannah , Dendroaspis polylepis , Naja kaouthia , Naja haje and Bungarus multicinctus ). The methodology demonstrated that the AChBP is able to effectively bind long-chain 3FTxs with relatively high affinity, but has low or no binding affinity towards short-chain 3FTxs, and as such provides an efficient analytical platform to investigate binding affinity of 3FTxs to the AChBP and mutants thereof and to rapidly identify bound toxins.
Keywords	snake venom ; neurotoxicity ; AChBP bioassay ; three-finger toxins ; nanofractionation ; elapid venom profiling ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	540
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Analytical Size Exclusion Chromatography Coupled with Mass Spectrometry in Parallel with High-Throughput Venomics and Bioassaying for Venom Profiling.

Terzioglu, Sedef / Bittenbinder, Mátyás A / Slagboom, Julien / van de Velde, Bas / Casewell, Nicholas R / Kool, Jeroen

Toxins

2023 Volume 15, Issue 9

Abstract: Modern analytical size exclusion chromatography (SEC) is a suitable technique to separate venom toxin families according to their size characteristics. In this study, a method was developed to separate intact venom toxins ... ...

Abstract	Modern analytical size exclusion chromatography (SEC) is a suitable technique to separate venom toxin families according to their size characteristics. In this study, a method was developed to separate intact venom toxins from
MeSH term(s)	Chromatography, Gel ; Anticoagulants ; Biological Assay ; Mass Spectrometry ; Viper Venoms
Chemical Substances	Anticoagulants ; Viper Venoms
Language	English
Publishing date	2023-09-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins15090552
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Article ; Online: High-Throughput Venomics.

Slagboom, Julien / Derks, Rico J E / Sadighi, Raya / Somsen, Govert W / Ulens, Chris / Casewell, Nicholas R / Kool, Jeroen

Journal of proteome research

2023 Volume 22, Issue 6, Page(s) 1734–1746

Abstract: In this study, we present high-throughput (HT) venomics, a novel analytical strategy capable of performing a full proteomic analysis of a snake venom within 3 days. This methodology comprises a combination of RP-HPLC-nanofractionation analytics, mass ... ...

Abstract	In this study, we present high-throughput (HT) venomics, a novel analytical strategy capable of performing a full proteomic analysis of a snake venom within 3 days. This methodology comprises a combination of RP-HPLC-nanofractionation analytics, mass spectrometry analysis, automated in-solution tryptic digestion, and high-throughput proteomics. In-house written scripts were developed to process all the obtained proteomics data by first compiling all Mascot search results for a single venom into a single Excel sheet. Then, a second script plots each of the identified toxins in so-called Protein Score Chromatograms (PSCs). For this, for each toxin, identified protein scores are plotted on the
MeSH term(s)	Animals ; Proteomics/methods ; Snake Venoms/chemistry ; Snake Bites ; Bungarus/metabolism ; Viperidae/metabolism ; Elapid Venoms/chemistry
Chemical Substances	Snake Venoms ; Elapid Venoms
Language	English
Publishing date	2023-04-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/acs.jproteome.2c00780
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Article ; Online: Distinct cardiotoxic effects by venoms of a spitting cobra (Naja pallida) and a rattlesnake (Crotalus atrox) revealed using an ex vivo Langendorff heart model.

Vlasblom, Ronald / van Thiel, Jory / Bittenbinder, Matyas A / van Rhijn, Jon-Ruben / Drost, Rinske / Muis, Lotte / Slagboom, Julien / Salvatori, Daniela / Kool, Jeroen / Veldman, Robert Jan

Toxicon : official journal of the International Society on Toxinology

2024 Volume 240, Page(s) 107637

Abstract: Here we describe the acute myocardial effects of an elapid (red spitting cobra, Naja pallida) and a viper (western diamondback rattlesnake, Crotalus atrox) venom using an ex vivo heart model. Our results reveal two different pathophysiological ... ...

Abstract	Here we describe the acute myocardial effects of an elapid (red spitting cobra, Naja pallida) and a viper (western diamondback rattlesnake, Crotalus atrox) venom using an ex vivo heart model. Our results reveal two different pathophysiological trajectories that influence heart function and morphology. While cobra venom causes a drop in contractile force, rattlesnake venom causes enhanced contractility and frequency that coincides with differences in myocellular morphology. This highlights the medical complexity of snake venom-induced cardiotoxicity.
MeSH term(s)	Animals ; Naja ; Crotalus ; Cardiotoxicity ; Elapid Venoms/toxicity ; Elapidae ; Crotalid Venoms/toxicity ; Venomous Snakes
Chemical Substances	Elapid Venoms ; Crotalid Venoms
Language	English
Publishing date	2024-02-06
Publishing country	England
Document type	Journal Article
ZDB-ID	204479-1
ISSN	1879-3150 ; 0041-0101
ISSN (online)	1879-3150
ISSN	0041-0101
DOI	10.1016/j.toxicon.2024.107637
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Zs.A 501: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
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Article ; Online: High throughput identification of human monoclonal antibodies and heavy-chain-only antibodies to treat snakebite.

Slagboom, Julien / Lewis, Abigail H / Schouten, Wietse M / van Haperen, Rien / Veltman, Mieke / Bittenbinder, Mátyás A / Vonk, Freek J / Casewell, Nicholas R / Grosveld, Frank / Drabek, Dubravka / Kool, Jeroen

Toxicon: X

2024 Volume 21, Page(s) 100185

Abstract: Snakebite envenoming is a priority Neglected Tropical Disease that causes an estimated 81,000-135,000 fatalities each year. The development of a new generation of safer, affordable, and accessible antivenom therapies is urgently needed. With this goal in ...

Abstract	Snakebite envenoming is a priority Neglected Tropical Disease that causes an estimated 81,000-135,000 fatalities each year. The development of a new generation of safer, affordable, and accessible antivenom therapies is urgently needed. With this goal in mind, rigorous characterisation of the specific toxins in snake venom is key to generating novel therapies for snakebite. Monoclonal antibodies directed against venom toxins are emerging as potentially strong candidates in the development of new snakebite diagnostics and treatment. Venoms comprise many different toxins of which several are responsible for their pathological effects. Due to the large variability of venoms within and between species, formulations of combinations of human antibodies are proposed as the next generation antivenoms. Here a high-throughput screening method employing antibody-based ligand fishing of venom toxins in 384 filter-well plate format has been developed to determine the antibody target/s The approach uses Protein G beads for antibody capture followed by exposure to a full venom or purified toxins to bind their respective ligand toxin(s). This is followed by a washing/centrifugation step to remove non-binding toxins and an in-well tryptic digest. Finally, peptides from each well are analysed by nanoLC-MS/MS and subsequent Mascot database searching to identify the bound toxin/s for each antibody under investigation. The approach was successfully validated to rapidly screen antibodies sourced from hybridomas, derived from venom-immunised mice expressing either regular human antibodies or heavy-chain-only human antibodies (HCAbs).
Language	English
Publishing date	2024-02-16
Publishing country	England
Document type	Journal Article
ISSN	2590-1710
ISSN (online)	2590-1710
DOI	10.1016/j.toxcx.2024.100185
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Article ; Online: A Combined Bioassay and Nanofractionation Approach to Investigate the Anticoagulant Toxins of Mamba and Cobra Venoms and Their Inhibition by Varespladib.

Arrahman, Arif / Kazandjian, Taline D / Still, Kristina B M / Slagboom, Julien / Somsen, Govert W / Vonk, Freek J / Casewell, Nicholas R / Kool, Jeroen

Toxins

2022 Volume 14, Issue 11

Abstract: Envenomation by elapid snakes primarily results in neurotoxic symptoms and, consequently, are the primary focus of therapeutic research concerning such venoms. However, mounting evidence suggests these venoms can additionally cause coagulopathic symptoms, ...

Abstract	Envenomation by elapid snakes primarily results in neurotoxic symptoms and, consequently, are the primary focus of therapeutic research concerning such venoms. However, mounting evidence suggests these venoms can additionally cause coagulopathic symptoms, as demonstrated by some Asian elapids and African spitting cobras. This study sought to investigate the coagulopathic potential of venoms from medically important elapids of the genera
MeSH term(s)	Animals ; Dendroaspis ; Anticoagulants/toxicity ; Proteomics ; Elapid Venoms/toxicity ; Elapidae ; Snake Venoms ; Phospholipases A2/toxicity ; Biological Assay ; Metalloproteases ; Antivenins/pharmacology
Chemical Substances	varespladib (2Q3P98DATH) ; marimastat (D5EQV23TDS) ; Anticoagulants ; Elapid Venoms ; Snake Venoms ; Phospholipases A2 (EC 3.1.1.4) ; Metalloproteases (EC 3.4.-) ; Antivenins
Language	English
Publishing date	2022-10-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins14110736
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