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Examples of the two most medically significant and speciose families of the front-fanged snakes. A An Elapid, an Australian coastal taipan (Oxyuranus scutellatus), and B a viper, a Sonoran desert sidewinder (Crotalus cerastes cercobombus). Note the large opening below and in front of the eye of the viper. This is an infra-red sensing pit, neurally integrated with the eye and allowing vision in the infra-red spectrum and distinguishes “pit vipers” Crotalinae, from “true vipers” Viperinae, the two major subfamilies of the family Viperidae. Photos courtesy of Shane Black (A), and Ross McGibbon (B)
Source publication
Snake venoms are heterogeneous mixtures of proteins and peptides used for prey subjugation. With modern proteomics there has been a rapid expansion in our knowledge of snake venom composition, resulting in the venom proteomes of 30% of vipers and 17% of elapids being characterised. From the reasonably complete proteomic coverage of front-fanged sna...
Citations
... Deinagkistrodon acutus, also named as Agkistrodon acutus, is one of the hypertoxic snakes in China [6]. The venom of Deinagkistrodon acutus are heterogeneous mixtures of proteins or peptides that act on prey synergistically [7]. ...
... Jin H and coworkers found that the most abundant constituent of the Deinagkistrodon acutus venom was phospholipases A2 (30.0%), snaclec (21.0%), antithrombin (17.8%), thrombin (8.1%) and metalloproteinases (4.2%) [8]. Deinagkistrodon acutus phospholipases A2 (dPLA2) that calcium ion dependent plays an essential role in the pathological process on the patient [7] [9]. Since this protease catalyzes the hydrolysis of the fatty acid ester at the sn-2 position of phospholipids releasing lysophospholipids and fatty acids [10] [11], and exerts a wide variety of relevant toxic actions such as myotoxic, neurotoxic, cardiotoxic, anticoagulant, cytotoxic, edematogenic, and proinflammatory effects [12] [13]. ...
Phospholipase A2 (PLA2) is the key enzyme to the venom from Deinagki-strodon acutus which is one of the highly venomous snakes in China. In addition to being a catalyst for the hydrolysis of phospholipases A2 from snake venom, it's well known that it possesses a broad spectrum of pharmacological activities, such as myotoxicity, neurotoxicity, cardiotoxicity, and hemolytic, anticoagulant and antiplatelet activities. However, snakebites are not efficiently treated by conventional serum therapy. Acute wounds can still cause poisoning and death. In order to find effective inhibitors of Deinagkistrodon venom acid phospholipase A2 (dPLA2), we obtained 385 compounds in 9 Chinese herbs from the TCMSP. These compounds were further performed to virtual screen using in silico tools like ADMET analysis, molecular docking and molecular dynamics (MD) simulation. After Pharmacokinetics analysis, we found 7 candidate compounds. Besides, analysis of small molecule interactions with dPLA2 confirmed that the amino acid residues HIS47 and GLY29 are key targets. Because they bind not only to the natural substrate phosphatidylcho-line and compounds known for having inhibitory functions, but also for combining with potential antidote molecules in Chinese herbal medicine. This study is the first to report experience with virtual screening for possible inhi-bitor of dPLA2, such as the interaction spatial structure, binding energy and binding interaction analysis, these experiences not only provide reference for further experimental research, but also have a guideline for the study of drug molecular mechanism of action.
... Snake venoms are complex mixtures of primarily peptides and proteins that are harmful to the human body, and especially the neuromuscular and circulatory systems [17,18]. Snake venom composition varies with a number of factors such as age, diet, geographic location, and seasonal changes [18,19], and is still far from being fully elucidated (for introduction and overview, see [18,20]). We analyzed the venom of E. ocellatus available to us for proteases, which might act on DBK. ...
The vasoactive peptide bradykinin (BK) is an important member of the renin–angiotensin system. Its discovery is tightly interwoven with snake venom research, because it was first detected in plasma following the addition of viper venom. While the fact that venoms liberate BK from a serum globulin fraction is well described, its destruction by the venom has largely gone unnoticed. Here, BK was found to be cleaved by snake venom metalloproteinases in the venom of Echis ocellatus, one of the deadliest snakes, which degraded its dabsylated form (DBK) in a few minutes after Pro7 (RPPGFSP↓FR). This is a common cleavage site for several mammalian proteases such as ACE, but is not typical for matrix metalloproteinases. Residual protease activity < 5% after addition of EDTA indicated that DBK is also cleaved by serine proteases to a minor extent. Mass spectrometry-based protein analysis provided spectral proof for several peptides of zinc metalloproteinase-disintegrin-like Eoc1, disintegrin EO4A, and three serine proteases in the venom.
... Specifically, the human relationship with snakes varies widely across cultures and contexts. While some cultures regard snakes as symbols of danger or malevolence, others regard them as symbols of fertility, healing, or spiritual significance, highlighting the Journal of Language and Literature ISSN: 1410-5691 (print); 2580-5878 (online) Mlamli Diko multifacetedness of this relationship (Tasoulis & Isbister, 2023). They highlight the amaXhosa society's inveterate cognizance of their ecological contexts. ...
Whereas amaXhosa literature continues to receive scholarly consideration, there is a deficit regarding scrutinizing amaXhosa folktales, particularly through the ecocriticism theory. As a result of this, there is an asymmetrical understanding of how ecosystems can be integrated into amaXhosa literature to advance the meaning of folktales in addition to the reality that folktales contain didactic and pedagogical components. It stands to reason, therefore, to channel heightened deliberation on amaXhosa folktales as part of oral literature. Given this fact, this article aims to examine how one selected amaXhosa folktale fuses ecological features into its pursuits to promote educational understanding among children and adults. Over and above this, the aim is to demonstrate how important it is to heed the instructional values of those with wisdom as it is pertinent in this particular folktale. The objective is to underline that amaXhosa folktales, as part of oral literature, continue to be applicable and as a result, they ought to be uncovered in the arena of scholarly discourse. The selected folktale, UNtando noNontando (Ntando and Nontando) is appreciated herein as a primary source of data, while ecocriticism is applied as a theory of interpretation and analysis. The findings and discussions indicate that this particular folktale advances the idea that humans, nature and animals are symbiotic and interactive in the environmental setting. Nevertheless, humans ought to respect the territories of animals and nature in a bid to create a proportioned society. The concluding remarks of this article present possible avenues for future scholarly discourses.
... A notable amount of glutathione peroxidase protein (GPx) was identified in all groups, comprising a significant percentage (2.5-4.5%) of the total proteins in the tested venoms. It is an unexpected result as GPx has been classified as a rare protein family and is usually identified in a minor amount [24]. Within the KwaZulu-Natal group, a considerable proportion of proteins from the immunoglobulin-like domain containing (Ig-like) group were detected (~3.5%), consistent with our previous reports for different venoms from Naja genus, where this group of proteins was also identified [15,[25][26]. ...
... This cluster is formed by the proteins markedly increased in KwaZulu-Natal venom samples, and it includes 21 proteins belonging to the 'Immunoglobulin-like domain superfamily' (IPR 036179). While these proteins are not officially recognized as known venom components [24], our previous reports have detected them [15,[25][26]. This analysis indicates they constitute nearly 4% of all venom proteins in the KwaZulu-Natal venom and around 0.6-0.7% in two others. ...
... In the case of two other antivenoms, a significantly lower number of signals in this region may indicate that some proteoforms may not be effectively bound. That could be at least partly attributed to the fact that the Antivipmyn Africa antivenom has been formulated using a higher number of venoms from vipers (Table 1), which typically contains a higher proportion of these proteins compared to elapids [16,24]. A similar trend is observed for specific phospholipases A 2 , where stronger signals appeared on membranes incubated with EchiTAb+ICP antivenom. ...
Background
Intraspecific variations in snake venom composition have been extensively documented, contributing to the diverse clinical effects observed in envenomed patients. Understanding these variations is essential for developing effective snakebite management strategies and targeted antivenom therapies. We aimed to comprehensively investigate venoms from three distinct populations of N . mossambica from Eswatini, Limpopo, and KwaZulu-Natal regions in Africa in terms of their protein composition and reactivity with three commercial antivenoms (SAIMR polyvalent, EchiTAb+ICP, and Antivipmyn Africa).
Methodology/Principal findings
Naja mossambica venoms from Eswatini region exhibited the highest content of neurotoxic proteins, constituting 20.70% of all venom proteins, compared to Limpopo (13.91%) and KwaZulu-Natal (12.80%), and was characterized by the highest diversity of neurotoxic proteins, including neurotoxic 3FTxs, Kunitz-type inhibitors, vespryns, and mamba intestinal toxin 1. KwaZulu-Natal population exhibited considerably lower cytotoxic 3FTx, higher PLA 2 content, and significant diversity in low-abundant proteins. Conversely, Limpopo venoms demonstrated the least diversity as demonstrated by electrophoretic and mass spectrometry analyses.
Immunochemical assessments unveiled differences in venom-antivenom reactivity, particularly concerning low-abundance proteins. EchiTAb+ICP antivenom demonstrated superior reactivity in serial dilution ELISA assays compared to SAIMR polyvalent.
Conclusions/Significance
Our findings reveal a substantial presence of neurotoxic proteins in N . mossambica venoms, challenging previous understandings of their composition. Additionally, the detection of numerous peptides aligning to uncharacterized proteins or proteins with unknown functions underscores a critical issue with existing venom protein databases, emphasizing the substantial gaps in our knowledge of snake venom protein components. This underscores the need for enhanced research in this domain. Moreover, our in vitro immunological assays suggest EchiTAb+ICP’s potential as an alternative to SAIMR antivenom, requiring confirmation through prospective in vivo neutralization studies.
... Snake venom consists of a complex and diverse mixture of proteins, with snake venom metalloproteases (SVMPs) being among the major components [5][6][7]. SVMPs are implicated in degrading basement membrane proteins, particularly collagen, surrounding tissues at the site of a snakebite [8]. These proteins typically have a molecular mass ranging from 20 to 100 kDa [1] and are categorized into three classes (P-I to P-III) based on the presence of accessory domains to the proteolytic domain [9][10][11]. ...
... O veneno de serpentes consiste em uma complexa combinação de moléculas bioativas, como enzimas, proteínas e peptídeos, as quais, ao entrarem em contato com suas presas, podem desencadear diversas atividades biológicas, incluindo neurotoxicidade, citotoxicidade, cardiotoxicidade, miotoxicidade e outras manifestações (Chan et al., 2016). Essa composição pode variar de acordo com a família, gênero e/ou espécie, sendo os principais alvos de estudo as serpentes das famílias Elapidae e Viperidae, em especial a Bothrops (Oliveira et al., 2022;Tasoulis;Isbister, 2023 (Diniz-Sousa et al., 2023), podendo o seu envenenamento causar efeitos locais e sistêmicos, bem como levar o paciente ao óbito (Brasil, 2013). Isso ocorre devido à rica composição molecular existente em seu veneno (Tasoulis;Isbister, 2023;Oliveira et al., 2022;Chan et al., 2016). ...
... O veneno de serpentes consiste em uma complexa combinação de moléculas bioativas, como enzimas, proteínas e peptídeos, as quais, ao entrarem em contato com suas presas, podem desencadear diversas atividades biológicas, incluindo neurotoxicidade, citotoxicidade, cardiotoxicidade, miotoxicidade e outras manifestações (Chan et al., 2016). Essa composição pode variar de acordo com a família, gênero e/ou espécie, sendo os principais alvos de estudo as serpentes das famílias Elapidae e Viperidae, em especial a Bothrops (Oliveira et al., 2022;Tasoulis;Isbister, 2023 (Diniz-Sousa et al., 2023), podendo o seu envenenamento causar efeitos locais e sistêmicos, bem como levar o paciente ao óbito (Brasil, 2013). Isso ocorre devido à rica composição molecular existente em seu veneno (Tasoulis;Isbister, 2023;Oliveira et al., 2022;Chan et al., 2016). ...
... Essa composição pode variar de acordo com a família, gênero e/ou espécie, sendo os principais alvos de estudo as serpentes das famílias Elapidae e Viperidae, em especial a Bothrops (Oliveira et al., 2022;Tasoulis;Isbister, 2023 (Diniz-Sousa et al., 2023), podendo o seu envenenamento causar efeitos locais e sistêmicos, bem como levar o paciente ao óbito (Brasil, 2013). Isso ocorre devido à rica composição molecular existente em seu veneno (Tasoulis;Isbister, 2023;Oliveira et al., 2022;Chan et al., 2016). ...
O objetivo do presente estudo foi realizar um levantamento tecnológico de documentos de patentes relacionadas às serpentes do gênero Bothrops sp., analisando os documentos relacionados para fins medicinais. Para a execução deste levantamento, foi utilizada a base de patentes Orbit Intelligence, buscando o termo “Bothrops” e direcionando a busca para fins medicinais usando a classificação de patentes A61K, sem delimitação temporal ou espacial. Foram encontradas 67 famílias de patentes, as quais possuem Brasil, China e México como os países com as maiores quantidades de depósitos de documentos de patentes. As principais instituições depositantes dos pedidos de patente foram a empresa suíça Pentapharm, a empresa brasileira Biolab Sanus Farmacêutica e a Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). Os principais países depositantes foram o Brasil, a China e o México. Foi possível notar um predomínio de patentes mortas, arquivadas por motivos diversos, em relação às vivas (depositadas e/ou concedidas), indicando que se trata de uma área tecnológica com baixa dinâmica de inovação.
... Recently, Tasoulis and Isbister (2023) presented an important review of the chemical composition of snake venoms, classifying the main families of proteins into two large groups: dominant and secondary. The first compounds of the four families of dominant proteins-phospholipases A 2 (PLA 2 ), snake venom metalloproteinases (SVMPs), three-finger toxins (3FTxs), and snake venom serine proteases (SVSPs)-are particularly relevant in the context of SBE, and six other families are of secondary importance in the composition of the venom: L-amino acid oxidases (LAAOs), cysteine-rich secretory proteins (CRiSPs), C-type lectins (CTLs), disintegrins (DIS), Kunitz peptides (KUN) and natriuretic peptides (NPs). ...
... Hyaluronidases are low-abundant enzymes (~52-55 kDa) found in elapid, viperid and some colubrid venoms 54,70,89 . Their main activity is the hydrolysis of hyaluronic acid, one of the key components of the ECM, and therefore contributes to ECM degradation 90,91 . ...
Snakebite envenoming is an important public health issue responsible for mortality and severe morbidity. Where mortality is mainly caused by venom toxins that induce cardiovascular disturbances, neurotoxicity, and acute kidney injury, morbidity is caused by toxins that directly or indirectly destroy cells and degrade the extracellular matrix. These are referred to as ‘tissue-damaging toxins’ and have previously been classified in various ways, most of which are based on the tissues being affected (e.g., cardiotoxins, myotoxins). This categorisation, however, is primarily phenomenological and not mechanistic. In this review, we propose an alternative way of classifying cytotoxins based on their mechanistic effects rather than using a description that is organ- or tissue-based. The mechanisms of toxin-induced tissue damage and their clinical implications are discussed. This review contributes to our understanding of fundamental biological processes associated with snakebite envenoming, which may pave the way for a knowledge-based search for novel therapeutic options.
... Snake venoms are cocktails of proteins, peptides, low-molecular-weight organics, and salts [1]. To be effective, they target the most vitally important systems of prey organisms, with the cardiovascular system being one of them [2,3]. ...
Phospholipases A2 (PLA2s) are a large family of snake toxins manifesting diverse biological effects, which are not always related to phospholipolytic activity. Snake venom PLA2s (svPLA2s) are extracellular proteins with a molecular mass of 13–14 kDa. They are present in venoms in the form of monomers, dimers, and larger oligomers. The cardiovascular system is one of the multiple svPLA2 targets in prey organisms. The results obtained previously on the cardiovascular effects of monomeric svPLA2s were inconsistent, while the data on the dimeric svPLA2 crotoxin from the rattlesnake Crotalus durissus terrificus showed that it significantly reduced the contractile force of guinea pig hearts. Here, we studied the effects of the heterodimeric svPLA2 HDP-1 from the viper Vipera nikolskii on papillary muscle (PM) contractility and the tension of the aortic rings (ARs). HDP-1 is structurally different from crotoxin, and over a wide range of concentrations, it produced a long-term, stable, positive inotropic effect in PMs, which did not turn into contractures at the concentrations studied. This also distinguishes HDP-1 from the monomeric svPLA2s, which at high concentrations inhibited cardiac function. HDP-1, when acting on ARs preconstricted with 10 μM phenylephrine, induced a vasorelaxant effect, similar to some other svPLA2s. These are the first indications of the cardiac and vascular effects of true vipers’ heterodimeric svPLA2s.
... The specific composition of venom can vary based on factors such as the species of snake, environmental conditions, age, sex, and the sort of prey that is accessible [6]. Snake venom is primarily composed of a variety of components, with bioactive peptides and proteins being the most abundant [7]. Aside from these, lipids, amino acids, carbohydrates, metal ions, nucleosides, and amines can constitute up 5%-10% of snake venom crude [8]. ...
... Most snake toxins are in the mass range of 4 to 100 kDa, while a number of multimeric toxins may exceed a total mass of 250 kDa [8]. Studies have demonstrated the categorization of snake venom protein families into different hierarchical groups based on their occurrence and abundance [7]. Based on a comprehensive analysis of the proteome composition of venom from 179 species (including 68 elapids and 111 vipers), 42 different protein families have been found [7]. ...
... Studies have demonstrated the categorization of snake venom protein families into different hierarchical groups based on their occurrence and abundance [7]. Based on a comprehensive analysis of the proteome composition of venom from 179 species (including 68 elapids and 111 vipers), 42 different protein families have been found [7]. ...
