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Naja nivea (Cape Cobra) is endemic to southern Africa. Envenoming by N. nivea is neurotoxic, resulting in fatal paralysis. Its venom composition, however, has not been studied in depth, and specific antivenoms against it remain limited in supply. Applying a protein decomplexation approach, this study unveiled the venom proteome of N. nivea from Sou...
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Context 1
... between the profiles ( Figure 4A-C), proteins in RP-HPLC fractions 1, 2, and 3, as well as the tailing fraction 12, were most markedly immunocaptured by VAPAV, whereas proteins in fractions 4-8 were least immunoretained. The degrees of immunoretention of venom proteins in these fractions were tabulated as percentages in Table 3. Accordingly, the VAPAV affinity column efficiently immunorecognized venom proteins in fractions 1, 2, and 3 (68-70% immunoretention). ...Context 2
... between the profiles ( Figure 4A-C), proteins in RP-HPLC fractions 1, 2, and 3, as well as the tailing fraction 12, were most markedly immunocaptured by VAPAV, whereas proteins in fractions 4-8 were least immunoretained. The degrees of immunoretention of venom proteins in these fractions were tabulated as percentages in Table 3. Accordingly, the VAPAV affinity column efficiently immunorecognized venom proteins in fractions 1, 2, and 3 (68-70% immunoretention). ...Similar publications
Snake venoms possess a range of pharmacological and toxicological activities. Here we evaluated the antibacterial and anti-biofilm activity against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) of venoms from the Samar spitting cobra Naja samarensis and the Puff adder Bitis arietans. Both venoms prevented b...
Citations
... One of these cobras is the Cape Cobra, Naja nivea (N. nivea), a non-spitting cobra that is found largely in the Cape of South Africa [6][7][8][9][10][11][12][13][14]. N. nivea envenomation is often fatal due to the rapid onset of respiratory paralysis, a symptom that can be attributed to the large number of small neurotoxins found in this venom [14,15]. ...
... nivea), a non-spitting cobra that is found largely in the Cape of South Africa [6][7][8][9][10][11][12][13][14]. N. nivea envenomation is often fatal due to the rapid onset of respiratory paralysis, a symptom that can be attributed to the large number of small neurotoxins found in this venom [14,15]. Despite its high level of medical importance, there has been a lack of research into the venom of N. nivea, with the majority of studies being single toxin studies from the 1970s-1980s [15][16][17][18][19][20]. ...
... Despite its high level of medical importance, there has been a lack of research into the venom of N. nivea, with the majority of studies being single toxin studies from the 1970s-1980s [15][16][17][18][19][20]. In 2022, Tan et al. [14]. published the first full venom proteome of N. nivea; however, due to well-reported differences in venom proteomes within snakes of the same species, it is important to continue efforts to characterise N. nivea venom to gain a more thorough understanding of its proteome [8][9][10][11][12][13][14]. ...
Naja nivea (N. nivea) is classed as a category one snake by the World Health Organization since its envenomation causes high levels of mortality and disability annually. Despite this, there has been little research into the venom composition of N. nivea, with only one full venom proteome published to date. Our current study separated N. nivea venom using size exclusion chromatography before utilizing a traditional bottom-up proteomics approach to unravel the composition of the venom proteome. As expected by its clinical presentation, N. nivea venom was found to consist mainly of neurotoxins, with three-finger toxins (3FTx), making up 76.01% of the total venom proteome. Additionally, cysteine-rich secretory proteins (CRISPs), vespryns (VESPs), cobra venom factors (CVFs), 5′-nucleotidases (5′NUCs), nerve growth factors (NGFs), phospholipase A2s (PLA2), acetylcholinesterases (AChEs), Kunitz-type serine protease inhibitor (KUN), phosphodiesterases (PDEs), L-amino acid oxidases (LAAOs), hydrolases (HYDs), snake venom metalloproteinases (SVMPs), and snake venom serine protease (SVSP) toxins were also identified in decreasing order of abundance. Interestingly, contrary to previous reports, we find PLA2 toxins in N. nivea venom. This highlights the importance of repeatedly profiling the venom of the same species to account for intra-species variation. Additionally, we report the first evidence of covalent protein complexes in N. nivea venom, which likely contribute to the potency of this venom.
... Nevertheless, their efficacy is limited to venoms antigenically similar to those used as immunogens to stimulate the immune response in animals used to manufacture the antivenom [5,9,[18][19][20][21]. Hence, to ensure a wide coverage of neutralization without requiring the identification of the offending snake species, the use of polyspecific formulations is preferred [2,18]. ...
... The selection of venoms used as immunogen to produce polyspecific antivenoms is based on the variation/conservation of the antigenic characteristics of venoms of the medically most important snakes in the region where the antivenom is intended to be used. The selection of the most appropriate venoms for immunization should, therefore, be based on a detailed knowledge of the antigenic relatedness of venoms and the medical relevance of the species [2,5,9,[18][19][20][21]. This represents a challenge in African cobra venoms, due to the abundance, diversity, and wide distribution of species [3]. ...
... The proteomic analyses of venoms of N. annulifera [6,8,9], N. ashei [7], N. haje [4,10], N. katiensis [10,36], N. melanoleuca [5], N. mossambica [8,36,37], N. nigricincta [37], N. nigricollis [10,36,38], N. nivea [21], and N. senegalensis [20] have been previously described. However, to the best of our knowledge, the complete proteomic or venom profiling analysis of N. anchietae venom has not been conducted even though this species poses a medical threat. ...
Background:
Envenomations by African snakes represent a high burden in the sub-Sahara region. The design and fabrication of polyspecific antivenoms with a broader effectiveness, specially tailored for its use in sub-Saharan Africa, require a better understanding of the immunological features of different Naja spp. venoms of highest medical impact in Africa; and to select the most appropriate antigen combinations to generate antivenoms of wider neutralizing scope.
Methodology/principal findings:
Rabbit-derived monospecific antisera were raised against the venoms of five spitting cobras and six non-spitting cobras. The effects of immunization in the animal model were assessed, as well as the development of antibody titers, as proved by immunochemical assays and neutralization of lethal, phospholipase A2 and dermonecrotic activities. By the end of the immunization schedule, the immunized rabbits showed normal values of all hematological parameters, and no muscle tissue damage was evidenced, although alterations in aspartate aminotransferase (AST) and alkaline phosphatase (ALP) suggested a degree of hepatic damage caused mainly by spitting cobra venoms. Immunologic analyses revealed a considerable extent of cross-reactivity of monospecific antisera against heterologous venoms within the spitting and no-spitting cobras, yet some antisera showed more extensive cross-reactivity than others. The antisera with the widest coverage were those of anti-Naja ashei and anti-N. nigricollis for the spitting cobras, and anti-N. haje and anti-N. senegalensis for the non-spitting cobras.
Conclusions/significance:
The methods and study design followed provide a rationale for the selection of the best combination of venoms for generating antivenoms of high cross-reactivity against cobra venoms in sub-Saharan Africa. Results suggest that venoms from N. ashei, N. nigricollis within the spitting cobras, and N. haje and N. senegalensis within the non-spitting cobras, generate antisera with a broader cross-reactivity. These experimental results should be translated to larger animal models used in antivenom elaboration to assess whether these predictions are reproduced.
... The available data suggest that the in vivo toxicity of CaTxs can vary quite a lot (e.g., [31]), but it may depend on many parameters, not only on the CaTx effects on the heart. It is even more difficult to interpret the changes that occur in the cardiovascular system when exposed to the whole venom since, in addition to cardiotoxins, cobra venom contains neurotoxins, PLA2, and many other components [32,33] which can affect the heart. In experiments on mice, the venom of the cobra N. sputatrix had a pronounced cardiotoxic effect, causing bradycardia, an increase in the amplitude of QRS complexes, and cardiac arrhythmias [34]. ...
Cardiotoxins (CaTx) of the three-finger toxin family are one of the main components of cobra venoms. Depending on the structure of the N-terminal or the central polypeptide loop, they are classified into either group I and II or P- and S-types, respectively, and toxins of different groups or types interact with lipid membranes variably. While their main target in the organism is the cardiovascular system, there is no data on the effects of CaTxs from different groups or types on cardiomyocytes. To evaluate these effects, a fluorescence measurement of intracellular Ca2+ concentration and an assessment of the rat cardiomyocytes’ shape were used. The obtained results showed that CaTxs of group I containing two adjacent proline residues in the N-terminal loop were less toxic to cardiomyocytes than group II toxins and that CaTxs of S-type were less active than P-type ones. The highest activity was observed for Naja oxiana cobra cardiotoxin 2, which is of P-type and belongs to group II. For the first time, the effects of CaTxs of different groups and types on the cardiomyocytes were studied, and the data obtained showed that the CaTx toxicity to cardiomyocytes depends on the structures both of the N-terminal and central polypeptide loops.
... Snake venom PLA2s (svPLA2s) exhibit a wide array of pharmacological activities, including myotoxicity, nephrotoxicity, anti-coagulant effects, and inflammation, owing to their structural versatility [56,57]. Used to be thought of as a ubiquitous group of enzymatic toxins in all snake venoms, svPLA2 abundances are now known to vary remarkably from a high of >60% in Russell's Viper venoms [58,59] to virtually none in the venoms of Naja nivea, Naja annulifera, and Naja senegalensis (subgenus: Uraeus) [60][61][62]. Previous studies showed C. rhodostoma venom has low PLA2 enzymatic activity [45,63], consistent with its proteome, in which PLA2 constitutes only 4.4% of the total venom proteins [18]. ...
In Southeast Asia, the Malayan Pit Viper (Calloselasma rhodostoma) is a venomous snake species of medical importance and bioprospecting potential. To unveil the diversity of its toxin genes, this study de novo assembled and analyzed the venom gland transcriptome of C. rhodostoma from Malaysia. The expression of toxin genes dominates the gland transcriptome by 53.78% of total transcript abundance (based on overall FPKM, Fragments Per Kilobase Million), in which 92 non-redundant transcripts belonging to 16 toxin families were identified. Snake venom metalloproteinase (SVMP, PI > PII > PIII) is the most dominant family (37.84% of all toxin FPKM), followed by phospholipase A2 (29.02%), bradykinin/angiotensin-converting enzyme inhibitor-C-type natriuretic peptide (16.30%), C-type lectin (CTL, 10.01%), snake venom serine protease (SVSP, 2.81%), L-amino acid oxidase (2.25%), and others (1.78%). The expressions of SVMP, CTL, and SVSP correlate with hemorrhagic, anti-platelet, and coagulopathic effects in envenoming. The SVMP metalloproteinase domains encode hemorrhagins (kistomin and rhodostoxin), while disintegrin (rhodostomin from P-II) acts by inhibiting platelet aggregation. CTL gene homologues uncovered include rhodocytin (platelet aggregators) and rhodocetin (platelet inhibitors), which contribute to thrombocytopenia and platelet dysfunction. The major SVSP is a thrombin-like enzyme (an ancrod homolog) responsible for defibrination in consumptive coagulopathy. The findings provide insight into the venom complexity of C. rhodostoma and the pathophysiology of envenoming.
... In this example, the total number of proteins was 38, which also served as the denominator. Naja nivea (South Africa) -9.0 75.7 Tan et al. (2022c) have venoms with exceptionally low PLA 2 activities, shown in both acidimetric and colorimetric assays. At a glance, svPLA 2 activities appear to be higher for cobras that exhibit venom-spitting behavior, which are also species known to possess cytotoxic venoms and clinically cause tissue necrosis, such as Naja sumatrana, and Naja nigricollis Warrell et al., 1976). ...
African cobras (Naja species) represent one of the most encountered medically important snakes in Africa. They are classified as African spitting (Afronaja subgenus) and non-spitting cobras (Uraeus and Boulengerina sub- genera) with similar and different characteristics. Snake venom toxins including three-finger toxin (3FTx), phospholipase A2 (PLA2), and snake venom metalloproteinase (SVMP) cause snakebite envenomation leading to morbidity and mortality. The profile of the proteome of African cobra venoms will help to develop safer and more effective antivenoms. The approval of Captopril by the US Food and Drug Administration (FDA) for the treatment of cardiovascular diseases, has led to intensified research towards possible use of venom toxins as therapeutics. In this review, we compare the venom proteome profile of 3 African Naja subgenera. In both Afronaja and Boulengerina subgenera, 3FTx (Afronaja–69.79%; Boulengerina–60.56%) followed by PLA2 (Afronaja–21.15%; Boulengerina–20.21%) dominated the venoms compared to the Uraeus subgenus dominated by 3FTx (84.55%) with little to no PLA2 abundance (0.8%). The venom of subgenus Uraeus was distinct from the other two subgenera by the almost total absence of PLA2, thus indicating little or no contribution of PLA2 in the envenomation caused by Uraeus compared to Afronaja and Boulengerina. Furthermore, we report studies on the experimental testing of African cobra venoms and toxins against diseases including anti-cancer properties.
Cytotoxins (CTs) are three-finger membrane-active toxins present mainly in cobra venom. Our analysis of the available CT amino acid sequences, literature data on their membrane activity, and conformational equilibria in aqueous solution and detergent micelles allowed us to identify specific amino acid residues which interfere with CT incorporation into membranes. They include Pro9, Ser28, and Asn/Asp45 within the N-terminal, central, and C-terminal loops, respectively. There is a hierarchy in the effect of these residues on membrane activity: Pro9 > Ser28 > Asn/Asp45. Taking into account all the possible combinations of special residues, we propose to divide CTs into eight groups. Group 1 includes toxins containing all of the above residues. Their representatives demonstrated the lowest membrane activity. Group 8 combines CTs that lack these residues. For the toxins from this group, the greatest membrane activity was observed. We predict that when solely membrane activity determines the cytotoxic effects, the activity of CTs from a group with a higher number should exceed that of CTs from a group with a lower number. This classification is supported by the available data on the cytotoxicity and membranotropic properties of CTs. We hypothesize that the special amino acid residues within the loops of the CT molecule may indicate their involvement in the interaction with non-lipid targets.
