scholarly journals Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom

Toxins ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 95 ◽  
Author(s):  
Choo Tan ◽  
Kae Tan ◽  
Tzu Ng ◽  
Evan Quah ◽  
Ahmad Ismail ◽  
...  
Keyword(s):  
Snake Venom ◽  
Serine Proteases ◽  
Cross Reactivity ◽  
Secretory Proteins ◽  
Proteomic Profiling ◽  
Phospholipases A2 ◽  
Central Highland ◽  
Liquid Chromatography Tandem Mass ◽  
Cameron Highlands ◽  
Venom Proteins

Trimeresurus nebularis is a montane pit viper that causes bites and envenomation to various communities in the central highland region of Malaysia, in particular Cameron’s Highlands. To unravel the venom composition of this species, the venom proteins were digested by trypsin and subjected to nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic profiling. Snake venom metalloproteinases (SVMP) dominated the venom proteome by 48.42% of total venom proteins, with a characteristic distribution of P-III: P-II classes in a ratio of 2:1, while P-I class was undetected. Snaclecs constituted the second most venomous protein family (19.43%), followed by snake venom serine proteases (SVSP, 14.27%), phospholipases A2 (5.40%), disintegrins (5.26%) and minor proteins including cysteine-rich secretory proteins, L-amino acid oxidases, phosphodiesterases, 5′-nucleotidases. The venomic profile correlates with local (painful progressive edema) and systemic (hemorrhage, coagulopathy, thrombocytopenia) manifestation of T. nebularis envenoming. As specific antivenom is unavailable for T. nebularis, the hetero-specific Thai Green Pit viper Monovalent Antivenom (GPVAV) was examined for immunological cross-reactivity. GPVAV exhibited good immunoreactivity to T. nebularis venom and the antivenom effectively cross-neutralized the hemotoxic and lethal effects of T. nebularis (lethality neutralizing potency = 1.6 mg venom per mL antivenom). The findings supported GPVAV use in treating T. nebularis envenoming.

scholarly journals Snake Venom Proteomics, Immunoreactivity and Toxicity Neutralization Studies for the Asiatic Mountain Pit Vipers, Ovophis convictus, Ovophis tonkinensis, and Hime Habu, Ovophis okinavensis

Toxins ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 514
Author(s):  
Choo Hock Tan ◽  
Praneetha Palasuberniam ◽  
Kae Yi Tan
Keyword(s):  
Snake Venom ◽  
Serine Proteases ◽  
Southern China ◽  
Snake Venoms ◽  
Phospholipases A2 ◽  
Limited Efficacy ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Species Specific ◽  
Venom Proteins

Snakebite envenomation is a serious neglected tropical disease, and its management is often complicated by the diversity of snake venoms. In Asia, pit vipers of the Ovophis species complex are medically important venomous snakes whose venom properties have not been investigated in depth. This study characterized the venom proteomes of Ovophis convictus (West Malaysia), Ovophis tonkinensis (northern Vietnam, southern China), and Ovophis okinavensis (Okinawa, Japan) by applying liquid chromatography-tandem mass spectrometry, which detected a high abundance of snake venom serine proteases (SVSP, constituting 40–60% of total venom proteins), followed by phospholipases A2, snake venom metalloproteinases of mainly P-III class, L-amino acid oxidases, and toxins from other protein families which were less abundant. The venoms exhibited different procoagulant activities in human plasma, with potency decreasing from O. tonkinensis > O. okinavensis > O. convictus. The procoagulant nature of venom confirms that consumptive coagulopathy underlies the pathophysiology of Ovophis pit viper envenomation. The hetero-specific antivenoms Gloydius brevicaudus monovalent antivenom (GbMAV) and Trimeresurus albolabris monovalent antivenom (TaMAV) were immunoreactive toward the venoms, and cross-neutralized their procoagulant activities, albeit at variably limited efficacy. In the absence of species-specific antivenom, these hetero-specific antivenoms may be useful in treating coagulotoxic envenomation caused by the different snakes in their respective regions.

scholarly journals Comprehensive Snake Venomics of the Okinawa Habu Pit Viper, Protobothrops flavoviridis, by Complementary Mass Spectrometry-Guided Approaches

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1893 ◽  
Author(s):  
Maik Damm ◽  
Benjamin-Florian Hempel ◽  
Ayse Nalbantsoy ◽  
Roderich Süssmuth
Keyword(s):  
Mass Spectrometry ◽  
Snake Venom ◽  
Serine Proteases ◽  
Secretory Proteins ◽  
Crude Venom ◽  
Human Neuroblastoma ◽  
Phospholipases A2 ◽  
Cytotoxicity Assays ◽  
Intact Mass ◽  
Snake Venomics

The Asian world is home to a multitude of venomous and dangerous snakes, which are used to induce various medical effects in the preparation of traditional snake tinctures and alcoholics, like the Japanese snake wine, named Habushu. The aim of this work was to perform the first quantitative proteomic analysis of the Protobothrops flavoviridis pit viper venom. Accordingly, the venom was analyzed by complimentary bottom-up and top-down mass spectrometry techniques. The mass spectrometry-based snake venomics approach revealed that more than half of the venom is composed of different phospholipases A2 (PLA2). The combination of this approach and an intact mass profiling led to the identification of the three main Habu PLA2s. Furthermore, nearly one-third of the total venom consists of snake venom metalloproteinases and disintegrins, and several minor represented toxin families were detected: C-type lectin-like proteins (CTL), cysteine-rich secretory proteins (CRISP), snake venom serine proteases (svSP), l-amino acid oxidases (LAAO), phosphodiesterase (PDE) and 5′-nucleotidase. Finally, the venom of P. flavoviridis contains certain bradykinin-potentiating peptides and related peptides, like the svMP inhibitors, pEKW, pEQW, pEEW and pENW. In preliminary MTT cytotoxicity assays, the highest cancerous-cytotoxicity of crude venom was measured against human neuroblastoma SH-SY5Y cells and shows disintegrin-like effects in some fractions.

Characterization of Venoms of Deinagkistrodon acutus and Bungarus multicinctus Using Proteomics and Peptidomics

2020 ◽  
Vol 17 (3) ◽  
pp. 241-254
Author(s):  
Yaqiong Zhang ◽  
Zhiping Jia ◽  
Yunyang Liu ◽  
Xinwen Zhou ◽  
Yi Kong
Keyword(s):  
Snake Venom ◽  
Protein Families ◽  
Traditional Medicines ◽  
Phospholipases A2 ◽  
Inhibitory Peptides ◽  
Sds Page ◽  
Deinagkistrodon Acutus ◽  
Venom Proteins ◽  
Proteins And Peptides

Background: Deinagkistrodon acutus (D. acutus) and Bungarus multicinctus (B. multicinctus) as traditional medicines have been used for hundreds of years in China. The venoms of these two species have strong toxicity on the victims. Objective: The objective of this study is to reveal the profile of venom proteins and peptides of D. acutus and B. multicinctus. Method: Ultrafiltration, SDS-PAGE coupled with in-gel tryptic digestion and Liquid Chromatography- Electrospray Ionization-Tandem Mass Spectrometry (LC-ESI-MS/MS) were used to characterize proteins and peptides of venoms of D. acutus and B. multicinctus. Results: In the D. acutus venom, 67 proteins (16 protein families) were identified, and snake venom metalloproteinases (SVMPs, 38.0%) and snake venom C-type lectins (snaclecs, 36.7%) were dominated proteins. In the B. multicinctus venom, 47 proteins (15 protein families) were identified, and three-finger toxins (3FTxs, 36.3%) and Kunitz-type Serine Protease Inhibitors (KSPIs, 32.8%) were major components. In addition, both venoms contained small amounts of other proteins, such as Snake Venom Serine Proteinases (SVSPs), Phospholipases A2 (PLA2s), Cysteine-Rich Secreted Proteins (CRISPs), 5'nucleotidases (5'NUCs), Phospholipases B (PLBs), Phosphodiesterases (PDEs), Phospholipase A2 Inhibitors (PLIs), Dipeptidyl Peptidases IV (DPP IVs), L-amino Acid Oxidases (LAAOs) and Angiotensin-Converting Enzymes (ACEs). Each venom also had its unique proteins, Nerve Growth Factors (NGFs) and Hyaluronidases (HYs) in D. acutus, and Cobra Venom Factors (CVFs) in B. multicinctus. In the peptidomics, 1543 and 250 peptides were identified in the venoms of D. acutus and B. multicinctus, respectively. Some peptides showed high similarity with neuropeptides, ACE inhibitory peptides, Bradykinin- Potentiating Peptides (BPPs), LAAOs and movement related peptides. Conclusion: Characterization of venom proteins and peptides of D. acutus and B. multicinctus will be helpful for the treatment of envenomation and drug discovery.

scholarly journals Cardiovascular Effects of Snake Toxins: Cardiotoxicity and Cardioprotection

Acta Naturae ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 4-14
Author(s):  
Alexey S. Averin ◽  
Yuri N. Utkin
Keyword(s):  
Cardiovascular System ◽  
Snake Venom ◽  
Antihypertensive Drugs ◽  
Cardiovascular Effects ◽  
Medical Application ◽  
New Drugs ◽  
Snake Venoms ◽  
Phospholipases A2 ◽  
Venom Proteins ◽  
Proteins And Peptides

Snake venoms, as complex mixtures of peptides and proteins, affect various vital systems of the organism. One of the main targets of the toxic components from snake venoms is the cardiovascular system. Venom proteins and peptides can act in different ways, exhibiting either cardiotoxic or cardioprotective effects. The principal classes of these compounds are cobra cardiotoxins, phospholipases A2, and natriuretic, as well as bradykinin-potentiating peptides. There is another group of proteins capable of enhancing angiogenesis, which include, e.g., vascular endothelial growth factors possessing hypotensive and cardioprotective activities. Venom proteins and peptides exhibiting cardiotropic and vasoactive effects are promising candidates for the design of new drugs capable of preventing or constricting the development of pathological processes in cardiovascular diseases, which are currently the leading cause of death worldwide. For example, a bradykinin-potentiating peptide from Bothrops jararaca snake venom was the first snake venom compound used to create the widely used antihypertensive drugs captopril and enalapril. In this paper, we review the current state of research on snake venom components affecting the cardiovascular system and analyse the mechanisms of physiological action of these toxins and the prospects for their medical application.

scholarly journals Cysteine-Rich Secretory Proteins (CRISPs) from Venomous Snakes: An Overview of the Functional Diversity in a Large and Underappreciated Superfamily

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 175 ◽  
Author(s):  
Takashi Tadokoro ◽  
Cassandra M. Modahl ◽  
Katsumi Maenaka ◽  
Narumi Aoki-Shioi
Keyword(s):  
Snake Venom ◽  
Inflammatory Responses ◽  
Neutrophil Infiltration ◽  
Secretory Proteins ◽  
Sequence Alignments ◽  
Functional Sites ◽  
Accelerated Evolution ◽  
Evolutionarily Conserved ◽  
Pathogenesis Related ◽  
Venom Proteins

The CAP protein superfamily (Cysteine-rich secretory proteins (CRISPs), Antigen 5 (Ag5), and Pathogenesis-related 1 (PR-1) proteins) is widely distributed, but for toxinologists, snake venom CRISPs are the most familiar members. Although CRISPs are found in the majority of venoms, very few of these proteins have been functionally characterized, but those that have been exhibit diverse activities. Snake venom CRISPs (svCRISPs) inhibit ion channels and the growth of new blood vessels (angiogenesis). They also increase vascular permeability and promote inflammatory responses (leukocyte and neutrophil infiltration). Interestingly, CRISPs in lamprey buccal gland secretions also manifest some of these activities, suggesting an evolutionarily conserved function. As we strive to better understand the functions that CRISPs serve in venoms, it is worth considering the broad range of CRISP physiological activities throughout the animal kingdom. In this review, we summarize those activities, known crystal structures and sequence alignments, and we discuss predicted functional sites. CRISPs may not be lethal or major components of venoms, but given their almost ubiquitous occurrence in venoms and the accelerated evolution of svCRISP genes, these venom proteins are likely to have functions worth investigating.

scholarly journals Proteomics and immunocharacterization of Asian mountain pit viper (Ovophis monticola) venom

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260496
Author(s):  
Siravit Sitprija ◽  
Lawan Chanhome ◽  
Onrapak Reamtong ◽  
Tipparat Thiangtrongjit ◽  
Taksa Vasaruchapong ◽  
...  
Keyword(s):  
Snake Venom ◽  
Serine Proteases ◽  
Indirect Elisa ◽  
Secretory Proteins ◽  
Acid Oxidase ◽  
Two Dimensional ◽  
Crude Venom ◽  
Amino Acid Oxidase ◽  
Specific Antigens ◽  
Phospholipases A

The venomic profile of Asian mountain pit viper Ovophis monticola is clarified in the present study. Using mass spectrometry-based proteomics, 247 different proteins were identified in crude venom of O. monticola found in Thailand. The most abundant proteins were snake venom metalloproteases (SVMP) (36.8%), snake venom serine proteases (SVSP) (31.1%), and phospholipases A2 (PLA2) (12.1%). Less abundant proteins included L-amino acid oxidase (LAAO) (5.7%), venom nerve growth factor (3.6%), nucleic acid degrading enzymes (3.2%), C-type lectins (CTL) (1.6%), cysteine-rich secretory proteins (CRISP) (1.2%) and disintegrin (1.2%). The immunoreactivity of this viper’s venom to a monovalent antivenom against green pit viper Trimeresurus albolabris, or to a polyvalent antivenom against hemotoxic venom was investigated by indirect ELISA and two-dimensional (2D) immunoblotting. Polyvalent antivenom showed substantially greater reactivity levels than monovalent antivenom. A titer for the monovalent antivenom was over 1:1.28x107 dilution while that of polyvalent antivenom was 1:5.12x107. Of a total of 89 spots comprising 173 proteins, 40 spots of predominantly SVMP, SVSP and PLA2 were specific antigens for antivenoms. The 49 unrecognized spots containing 72 proteins were characterized as non-reactive proteins, and included certain types of CTLs and CRISPs. These neglected venom constituents could limit the effectiveness of antivenom-based therapy currently available for victims of pit viper envenomation.

scholarly journals Focused Proteomics Analysis of Habu Snake (Protobothrops flavoviridis) Venom Using Antivenom-Based Affinity Chromatography Reveals Novel Myonecrosis-Enhancing Activity of Thrombin-Like Serine Proteases

2021 ◽  
Vol 12 ◽  
Author(s):  
Tomohisa Ogawa ◽  
Yu Tobishima ◽  
Shizuka Kamata ◽  
Youhei Matsuda ◽  
Koji Muramoto ◽  
...  
Keyword(s):  
Serine Protease ◽  
Snake Venom ◽  
Serine Proteases ◽  
Causes Of Death ◽  
Bioactive Peptides ◽  
Proteomics Analysis ◽  
Enhancing Factor ◽  
2D Gel ◽  
Venom Proteins

Snakebites are one of the major causes of death and long-term disability in the developing countries due to the presence of various bioactive peptides and proteins in snake venom. In Japan, the venom of the habu snake (Protobothrops flavoviridis) causes severe permanent damage due to its myonecrotic toxins. Antivenom immunoglobulins are an effective therapy for snakebites, and antivenom was recently developed with effective suppressive activity against myonecrosis induced by snake venom. To compare the properties of an antivenom having anti-myonecrotic activity with those of conventional antivenom with no anti-myonecrotic activity, this study applied focused proteomics analysis of habu venom proteins using 2D gel electrophoresis. As a target protein for antivenom immunoglobulins with anti-myonecrotic activity, we identified a thrombin-like serine protease, TLSP2 (TLf2), which was an inactive proteolytic isoform due to the replacement of the active site, His43 with Arg. Additionally, we identified the unique properties and a novel synergistic function of pseudoenzyme TLf2 as a myonecrosis-enhancing factor. To our knowledge, this is the first report of a function of a catalytically inactive snake serine protease.

scholarly journals Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders

2021 ◽  
Vol 22 (17) ◽  
pp. 9643
Author(s):  
Sébastien Larréché ◽  
Jean-Philippe Chippaux ◽  
Lucie Chevillard ◽  
Simon Mathé ◽  
Dabor Résière ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Snake Venom ◽  
Thrombotic Microangiopathy ◽  
Serine Proteases ◽  
Kidney Injury ◽  
Coagulation Factors ◽  
Cardiovascular Collapse ◽  
Cell Integrity ◽  
Consumption Coagulopathy ◽  
Phospholipases A2

Toxins from Bothrops venoms targeting hemostasis are responsible for a broad range of clinical and biological syndromes including local and systemic bleeding, incoagulability, thrombotic microangiopathy and macrothrombosis. Beyond hemostais disorders, toxins are also involved in the pathogenesis of edema and in most complications such as hypovolemia, cardiovascular collapse, acute kidney injury, myonecrosis, compartmental syndrome and superinfection. These toxins can be classified as enzymatic proteins (snake venom metalloproteinases, snake venom serine proteases, phospholipases A2 and L-amino acid oxidases) and non-enzymatic proteins (desintegrins and C-type lectin proteins). Bleeding is due to a multifocal toxicity targeting vessels, platelets and coagulation factors. Vessel damage due to the degradation of basement membrane and the subsequent disruption of endothelial cell integrity under hydrostatic pressure and tangential shear stress is primarily responsible for bleeding. Hemorrhage is promoted by thrombocytopenia, platelet hypoaggregation, consumption coagulopathy and fibrin(ogen)olysis. Onset of thrombotic microangiopathy is probably due to the switch of endothelium to a prothrombotic phenotype with overexpression of tissue factor and other pro-aggregating biomarkers in association with activation of platelets and coagulation. Thrombosis involving large-caliber vessels in B. lanceolatus envenomation remains a unique entity, which exact pathophysiology remains poorly understood.

Snake Venom Proteins Isolated from Tunisian Vipers: Pharmacological and Therapeutic Overview

2020 ◽  
Vol 01 ◽  
Author(s):  
Maram Morjen ◽  
Zaineb Abdelkafi-Koubaa ◽  
Jed Jebali ◽  
Erij Messadi ◽  
Najet Srairi-Abid ◽  
...  
Keyword(s):  
Snake Venom ◽  
Therapeutic Potential ◽  
Biological Effects ◽  
Basic Research ◽  
New Drugs ◽  
Phospholipases A2 ◽  
Potential Benefits ◽  
New Research ◽  
Endothelial Growth Factor ◽  
Venom Proteins

: The venoms of Tunisian wildlife snakes are complex mixtures containing proteins/peptides and non-protein molecules. Proteins and peptides are the most abundant compounds responsible for the biological effects of venoms. Snake venoms proteins have enzymatic or non-enzymatic activities, which are grouped into different families including C-type lectin proteins, disintegrins (long, medium and short disintegrins), Kunitz-type serine protease inhibitors, natriuretic-like peptides, vascular endothelial growth factor-related proteins, L-amino acid oxidases, phospholipases A2 and serine proteinases. With technological advancements, the toxic effects of venoms were turned into potential benefits for clinical diagnosis, basic research and development of new research tools and drugs of potential clinical use. Our research team has shown that Macrovipera lebetina and Cerastes cerastes venom components of Tunisian wildlife snakes had great potential for the development of new drugs for the treatment of cancer, angiogenesis disorders or cardiovascular diseases. This review is an overview on snake venom proteins from Macrovipera lebetina and Cerastes cerastes and their biochemical, pharmacological and molecular characterization and their importance as protein resources with therapeutic potential.

scholarly journals Protein Identification of Venoms of the African Spitting Cobras, Naja mossambica and Naja nigricincta nigricincta

Toxins ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 520
Author(s):  
Ottilie Katali ◽  
Loide Shipingana ◽  
Peter Nyarangó ◽  
Mirva Pääkkönen ◽  
Erastus Haindongo ◽  
...  
Keyword(s):  
High Performance ◽  
Protein Identification ◽  
Sodium Dodecyl ◽  
Secretory Proteins ◽  
Tandem Mass ◽  
Protein Families ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Fundamental Value ◽  
Venom Proteins

Cobra snakes, including Naja mossambica and Naja nigricincta nigricincta, are one of the major groups of snakes responsible for snakebites in southern Africa, producing significant cytotoxicity and tissue damage. The venom of N. mossambica has been briefly characterised, but that of N. n. nigricincta is not reported. The current study identifies the venom proteins of N. mossambica and N. n. nigricincta. This is achieved using sodium dodecyl sulphate (SDS)-polyacrylamide gel eletrophroresis (PAGE), followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Most of the proteins were less than 17 kDa in both snakes. N. mossambica was found to have 75 proteins in total (from 16 protein families), whereas N.n. nigricincta had 73 (from 16 protein families). Of these identified proteins, 57 were common in both snakes. The proteins identified belonged to various families, including the three-finger toxins (3FTx), Cysteine-rich secretory proteins (CRiSP), Phospholipase A2 (PLA2) and Venom metalloproteinase M12B (SVMP). The current study contributes to the profile knowledge of snake venom compositions, which is of fundamental value in understanding the proteins that play a major role in envenomation.

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