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  1. Immunoreactivity and neutralization capacity of Philippine cobra antivenom against Naja philippinensis and Naja samarensis venoms
    Tan CH, Palasuberniam P, Blanco FB, Tan KY
    Trans R Soc Trop Med Hyg, 2021 01 07;115(1):78-84.
    PMID: 32945886 DOI: 10.1093/trstmh/traa087
    BACKGROUND: The Philippine cobra (Naja philippinensis) and Samar cobra (Naja samarensis) are two WHO Category 1 medically important venomous snakes in the Philippines. Philippine cobra antivenom (PCAV) is the only antivenom available in the country, but its neutralization capacity against the venoms of N. philippinensis and hetero-specific N. samarensis has not been reported. This knowledge gap greatly hinders the optimization of antivenom use in the region.

    METHODS: This study examined the immunological binding and neutralization capacity of PCAV against the two cobra venoms using WHO-recommended protocols.

    RESULTS: In mice, both venoms were highly neurotoxic and lethal with a median lethal dose of 0.18 and 0.20 µg/g, respectively. PCAV exhibited strong and comparable immunoreactivity toward the venoms, indicating conserved venom antigenicity between the two allopatric species. In in vivo assay, PCAV was only moderately effective in neutralizing the toxicity of both venoms. Its potency was even lower against the hetero-specific N. samarensis venom by approximately two-fold compared with its potency against N. philippinensis venom.

    CONCLUSION: The results indicated that PCAV could be used to treat N. samarensis envenomation but at a higher dose, which might increase the risk of hypersensitivity and worsen the shortage of antivenom supply in the field. Antivenom manufacturing should be improved by developing a low-dose, high-efficacy product against cobra envenomation.

    Matched MeSH terms: Elapid Venoms*
  2. Enzymatic activities of Malayan cobra (Naja naja sputatrix) venoms
    Tan NH, Tan CS
    Toxicon, 1987;25(11):1249-53.
    PMID: 3433296
    The enzymatic activities of four samples of Malayan cobra venom were investigated. There was significant variation in the contents of L-amino acid oxidase, alkaline phosphomonoesterase, acetylcholinesterase, phospholipase A, 5'-nucleotidase and hyaluronidase. The phosphodiesterase content was, however, constant. Storage of the lyophilized venom powder at 25 degrees C for 1 month did not affect the enzymatic activities. The venom enzymatic activities were generally also stable at 4 degrees C in 0.85% saline solution. After incubation at 37 degrees C for 39 days in 0.85% saline solution, the venom still retained considerable amounts of enzymatic activities. SP-Sephadex C-25 ion-exchange chromatography of the venom showed that the phospholipase A, L-amino acid oxidase, 5'-nucleotidase, phosphodiesterase and alkaline phosphomonoesterase exist in multiple forms.
    Matched MeSH terms: Elapid Venoms/analysis*; Elapid Venoms/pharmacology
  3. A comparative study of the biological properties of Australian elapid venoms
    Tan NH, Ponnudurai G
    Comp Biochem Physiol C Comp Pharmacol Toxicol, 1990;97(1):99-106.
    PMID: 1981349
    1. The hemorrhagic, procoagulant, anticoagulant, protease, phosphodiesterase, alkaline phosphomonoesterase, L-amino acid oxidase, acetylcholinesterase, arginine ester hydrolase, phospholipase A, 5'-nucleotidase and hyaluronidase activities of 39 samples of venoms from 13 species (15 taxa) of Australian elapids were determined and the Sephadex G-75 gel filtration patterns for some of the venoms were also examined. 2. The results indicate that Australian elapid venoms can be divided into two groups: procoagulant Australian venoms (including N. scutatus, N. ater, O. scutellatus, O. microlepidotus, P. porphyriacus, T. carinatus, H. stephensii and P. textilis) and non-procoagulant Australian venoms (including A. superbus, P. colletti, P. australis, P. guttatus and A. antarcticus). 3. The non-procoagulant Australian venoms exhibited biological properties similar to other elapid venoms, while the procoagulant Australian venoms exhibited some properties characteristic of viperid venoms. 4. The data show that information on venom biological properties can be used for differentiation of many species of Australian elapids. 5. Particularly useful for this purpose are the hyaluronidase, alkaline phosphomonoesterase, acetylcholinesterase, and the procoagulant activities and the Sephadex G-75 gel filtration patterns of the venoms.
    Matched MeSH terms: Elapid Venoms/isolation & purification; Elapid Venoms/metabolism; Elapid Venoms/pharmacology; Elapid Venoms/toxicity*
  4. Fulltext Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan: Insights into Toxicity and Antivenom Neutralization
    Wong KY, Tan CH, Tan NH
    Am J Trop Med Hyg, 2016 06 01;94(6):1392-9.
    PMID: 27022154 DOI: 10.4269/ajtmh.15-0871
    Geographical variations of snake venoms can result in suboptimal effectiveness of Indian antivenoms that are currently used in most South Asian countries. This study investigated the toxicity and neutralization profile of the venom and toxins from Pakistani spectacled cobra, Naja naja, using VINS polyvalent antivenom (VPAV, India), Naja kaouthia monovalent antivenom (NKMAV, Thailand), and neuro bivalent antivenom (NBAV, Taiwan). Cation-exchange and reverse-phase high-performance liquid chromatography fractionations followed by toxin identification through liquid chromatography-mass spectrometry (MS)/MS indicated that the venom comprised mainly of postsynaptic neurotoxins (NTXs) (long neurotoxins [LNTXs], 28.3%; short neurotoxins [SNTXs], 8%), cytotoxins (CTXs) (31.2%), and acidic phospholipases A2 (12.3%). NKMAV is the most effective in neutralizing the lethal effect of the venom (potency = 1.1 mg venom/mL) and its LNTX (potency = 0.5 mg toxin/mL), consistent with the high content of LNTX in N. kaouthia venom. VPAV was effective in neutralizing the CTX (potency = 0.4 mg toxin/mL), in agreement with the higher CTX abundance in Indian cobra venom. All the three antivenoms were weak in neutralizing the SNTX (potency = 0.03-0.04 mg toxin/mL), including NBAV that was raised from the SNTX-rich Taiwanese cobra venom. In a challenge-rescue experiment, envenomed mice were prevented from death by a maximal dose of VPAV (intravenous 200 μL) but the recovery from paralysis was slow, indicating the need for higher or repeated doses of VPAV. Our results suggest that optimal neutralization for Pakistani N. naja venom may be achieved by improving the formulation of antivenom production to enhance antivenom immunoreactivity against long and SNTXs.
    Matched MeSH terms: Elapid Venoms/toxicity*; Elapid Venoms/chemistry
  5. Venomics of the beaked sea snake, Hydrophis schistosus: A minimalist toxin arsenal and its cross-neutralization by heterologous antivenoms
    Tan CH, Tan KY, Lim SE, Tan NH
    J Proteomics, 2015 Aug 3;126:121-30.
    PMID: 26047715 DOI: 10.1016/j.jprot.2015.05.035
    The venom proteome of Hydrophis schistosus (syn: Enhydrina schistosa) captured in Malaysian waters was investigated using reverse-phase HPLC, SDS-PAGE and high-resolution liquid chromatography-tandem mass spectrometry. The findings revealed a minimalist profile with only 18 venom proteins. These proteins belong to 5 toxin families: three-finger toxin (3FTx), phospholipase A2 (PLA2), cysteine-rich secretory protein (CRISP), snake venom metalloprotease (SVMP) and L-amino acid oxidase (LAAO). The 3FTxs (3 short neurotoxins and 4 long neurotoxins) constitute 70.5% of total venom protein, 55.8% being short neurotoxins and 14.7% long neurotoxins. The PLA2 family consists of four basic (21.4%) and three acidic (6.1%) isoforms. The minor proteins include one CRISP (1.3%), two SVMPs (0.5%) and one LAAO (0.2%). This is the first report of the presence of long neurotoxins, CRISP and LAAO in H. schistosus venom. The neurotoxins and the basic PLA2 are highly lethal in mice with an intravenous median lethal dose of <0.2 μg/g. Cross-neutralization by heterologous elapid antivenoms (Naja kaouthia monovalent antivenom and Neuro polyvalent antivenom) was moderate against the long neurotoxin and basic PLA2, but weak against the short neurotoxin, indicating that the latter is the limiting factor to be overcome for improving the antivenom cross-neutralization efficacy.
    Matched MeSH terms: Elapid Venoms/metabolism*; Elapid Venoms/toxicity
  6. The biological properties of venoms of some American coral snakes (Genus micrurus)
    Tan NH, Ponnudurai G
    Comp. Biochem. Physiol., B, 1992 Mar;101(3):471-4.
    PMID: 1582185
    1. The biological properties of nine venom samples from six taxa of Micrurus were investigated. The venoms exhibited low protease, phosphodiesterase and 5'-nucleotidase activities, moderate to strong phospholipase A and hyaluronidase activities, variable L-amino acid oxidase activity and were devoid of arginine ester hydrolase and thrombin-like activities. Some venom samples exhibited strong acetylcholinesterase activity. Venoms of M. c. dumerili and M. frontalis exhibited exceptionally high alkaline phosphomonoesterase activity while two of the M. f. fulvius venom samples tested exhibited strong hemorrhagic activity in mice. 2. The polyacrylamide gel electrophoretic patterns of the venoms indicate that most of the Micrurus venom proteins are basic proteins. All Micrurus venoms tested exhibited similar SDS-polyacrylamide gel electrophoretic patterns, with an intense low mol. wt protein band. 3. The Micrurus venoms appear to exhibit biological properties similar to other elapid venoms found in Asia and Africa. There are, however, no common characteristics in the biological properties of the venoms examined at the generic level.
    Matched MeSH terms: Elapid Venoms/enzymology*; Elapid Venoms/toxicity
  7. The lethal and biochemical properties of Bungarus candidus (Malayan krait) venom and venom fractions
    Tan NH, Poh CH, Tan CS
    Toxicon, 1989;27(9):1065-70.
    PMID: 2799837
    Bungarus candidus venom exhibited high hyaluronidase, acetylcholinesterase and phospholipase A activities; low proteinase, 5'-nucleotidase, alkaline phosphomonoesterase and phosphodiesterase activities and moderately high L-amino acid oxidase activity. SP-Sephadex C-50 ion exchange chromatographic fractionation of the venom and Sephadex G-50 chromatography of the major lethal venom fractions indicate that the venom contains at least two highly lethal, basic phospholipases A with LD50 (i.v.) values of 0.02 micrograms/g (F6A) and 0.18 micrograms/g (F4A), respectively; as well as two polypeptide toxins with LD50 (i.v.) values of 0.17 micrograms/g and 0.83 micrograms/g, respectively. The major lethal toxin is the basic lethal phospholipase A, F6A, which accounts for approximately 13% of the venom protein and has a mol. wt of 21,000.
    Matched MeSH terms: Elapid Venoms/analysis; Elapid Venoms/toxicity*
  8. Enzymatic and toxic properties of Ophiophagus hannah (king cobra) venom and venom fractions
    Tan NH, Hj MN
    Toxicon, 1989;27(6):689-95.
    PMID: 2749765
    Some enzymatic activities and toxic properties of four samples of Ophiophagus hannah (king cobra) venom were investigated. There is little intraspecific variation in enzyme contents, protein composition and toxic properties of the venom. The venom does not exhibit hemolytic or edema-inducing activity but is characterized by an exceptionally high alkaline phosphomonoesterase activity. DEAE-Sephacel ion exchange chromatography and Sephadex G-75 gel filtration chromatography of the venom indicate that the major lethal toxins are the low mol.wt, non-enzymatic basic proteins. Venom fractions exhibiting high enzymatic activities apparently do not play an important role in the lethality in mice of Ophiophagus hannah venom.
    Matched MeSH terms: Elapid Venoms/analysis; Elapid Venoms/toxicity*
  9. Geographical variations in king cobra (Ophiophagus hannah) venom from Thailand, Malaysia, Indonesia and China: On venom lethality, antivenom immunoreactivity and in vivo neutralization
    Tan KY, Ng TS, Bourges A, Ismail AK, Maharani T, Khomvilai S, et al.
    Acta Trop, 2020 Mar;203:105311.
    PMID: 31862461 DOI: 10.1016/j.actatropica.2019.105311
    The wide distribution of king cobra (Ophiophagus hannah), a medically important venomous snake in Asia could be associated with geographical variation in the toxicity and antigenicity of the venom. This study investigated the lethality of king cobra venoms (KCV) from four geographical locales (Malaysia, Thailand, Indonesia, China), and the immunological binding as well as in vivo neutralization activities of three antivenom products (Thai Ophiophagus hannah monovalent antivenom, OHMAV; Indonesian Serum Anti Bisa Ular, SABU; Chinese Naja atra monovalent antivenom, NAMAV) toward the venoms. The Indonesian and Chinese KCV were more lethal (median lethal dose, LD50 ~0.5 μg/g) than those from Malaysia and Thailand (LD50 ~1.0 μg/g). The antivenoms, composed of F(ab)'2, were variably immunoreactive toward the KCV from all locales, with OHMAV exhibited the highest immunological binding activity. In mice, OHMAV neutralized the neurotoxic lethality of Thai KCV most effectively (normalized potency = 118 mg venom neutralized per g antivenom) followed by Malaysian, Indonesian and Chinese KCV. In comparison, the hetero-specific SABU was remarkably less potent by at least 6 to10 folds, whereas NAMAV appeared to be non-effective. The finding supports that a specific king cobra antivenom is needed for the effective treatment of king cobra envenomation in each region.
    Matched MeSH terms: Elapid Venoms/immunology*; Elapid Venoms/toxicity*
  10. Fulltext Snake Venomics and Antivenomics of Cape Cobra (Naja nivea) from South Africa: Insights into Venom Toxicity and Cross-Neutralization Activity
    Tan CH, Wong KY, Huang LK, Tan KY, Tan NH, Wu WG
    Toxins (Basel), 2022 Dec 07;14(12).
    PMID: 36548757 DOI: 10.3390/toxins14120860
    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 South Africa. The major components in the venom are cytotoxins/cardiotoxins (~75.6% of total venom proteins) and alpha-neurotoxins (~7.4%), which belong to the three-finger toxin family. Intriguingly, phospholipase A2 (PLA2) was undetected-this is a unique venom phenotype increasingly recognized in the African cobras of the Uraeus subgenus. The work further showed that VINS African Polyvalent Antivenom (VAPAV) exhibited cross-reactivity toward the venom and immunorecognized its toxin fractions. In mice, VAPAV was moderately efficacious in cross-neutralizing the venom lethality with a potency of 0.51 mg/mL (amount of venom completely neutralized per milliliter of antivenom). In the challenge-rescue model, VAPAV prevented death in 75% of experimentally envenomed mice, with slow recovery from neurotoxicity up to 24 h. The finding suggests the potential para-specific utility of VAPAV for N. nivea envenoming, although a higher dose or repeated administration of the antivenom may be required to fully reverse the neurotoxic effect of the venom.
    Matched MeSH terms: Elapid Venoms/metabolism; Elapid Venoms/toxicity
  11. Proteomic analysis of Moroccan cobra Naja haje legionis venom using tandem mass spectrometry
    Malih I, Ahmad rusmili MR, Tee TY, Saile R, Ghalim N, Othman I
    J Proteomics, 2014 Jan 16;96:240-52.
    PMID: 24269350 DOI: 10.1016/j.jprot.2013.11.012
    The proteome of the venom of Naja haje legionis, the only medically important elapid species in Morocco, has been elucidated by using a combination of proteomic techniques that includes size exclusion chromatography, reverse-phase HPLC, Tricine/SDS-Page, tryptic digestion, Q-TOF tandem mass spectrometry and database search. The sequence analysis of venom fractions revealed a highly complex venom proteome which counts a total of 76 proteins identified from database that can be assigned into 9 proteins families. We report the identification of: cobra venom factor (CVF), l-amino-acid oxidases (LAAO), acetylcholinesterase (AChE), snake venom metalloproteinases (SVMP), cysteine rich secretory proteins (CRISP), venom nerve growth factor (vNGF), phospholipases A2 (PLA2), vespryns, kunitz-type inhibitor, short neurotoxins, long neurotoxins, weak neurotoxins, neurotoxin like proteins, muscarinic toxins, cardiotoxins and cytotoxins. Comparison of these proteins showed high sequence homology with proteins from other African and Asian cobras. Further works are needed to assess the contribution of individual toxins in venom toxicity.
    Matched MeSH terms: Elapid Venoms/metabolism*
  12. Genus Calliophis of Asiatic coral snakes: A deficiency of venom cross-reactivity and neutralization against seven regional elapid antivenoms
    Tan CH, Liew JL, Tan KY, Tan NH
    Toxicon, 2016 Oct;121:130-133.
    PMID: 27616455 DOI: 10.1016/j.toxicon.2016.09.003
    Venoms of Calliophis bivirgata and Calliophis intestinalis exhibited moderate binding activities toward Neuro Bivalent Antivenom (Taiwan) but not the other six elapid monovalent or bivalent antivenoms available in the region. All antivenoms failed to neutralize C. bivirgata venom lethality in mice. The findings indicate the need to validate antivenom cross-reactivity with in vivo cross-neutralization, and imply that distinct antigens of Calliophis venoms should be incorporated in the production of a pan-regional poly-specific antivenom.
    Matched MeSH terms: Elapid Venoms/immunology*
  13. Fulltext Proteomic Characterization of Two Medically Important Malaysian Snake Venoms, Calloselasma rhodostoma (Malayan Pit Viper) and Ophiophagus hannah (King Cobra)
    Kunalan S, Othman I, Syed Hassan S, Hodgson WC
    Toxins (Basel), 2018 Oct 26;10(11).
    PMID: 30373186 DOI: 10.3390/toxins10110434
    Calloselasma rhodostoma (CR) and Ophiophagus hannah (OH) are two medically important snakes found in Malaysia. While some studies have described the biological properties of these venoms, feeding and environmental conditions also influence the concentration and distribution of snake venom toxins, resulting in variations in venom composition. Therefore, a combined proteomic approach using shotgun and gel filtration chromatography, analyzed by tandem mass spectrometry, was used to examine the composition of venoms from these Malaysian snakes. The analysis revealed 114 proteins (15 toxin families) and 176 proteins (20 toxin families) in Malaysian Calloselasma rhodostoma and Ophiophagus hannah species, respectively. Flavin monoamine oxidase, phospholipase A₂, phosphodiesterase, snake venom metalloproteinase, and serine protease toxin families were identified in both venoms. Aminopeptidase, glutaminyl-peptide cyclotransferase along with ankyrin repeats were identified for the first time in CR venom, and insulin, c-type lectins/snaclecs, hepatocyte growth factor, and macrophage colony-stimulating factor together with tumor necrosis factor were identified in OH venom for the first time. Our combined proteomic approach has identified a comprehensive arsenal of toxins in CR and OH venoms. These data may be utilized for improved antivenom production, understanding pathological effects of envenoming, and the discovery of biologically active peptides with medical and/or biotechnological value.
    Matched MeSH terms: Elapid Venoms/chemistry*
  14. Preclinical assessment of VPEAV, a new trivalent antivenom for elapid snakebite envenoming in the Philippines: Proteomics, immunoreactivity and toxicity neutralization
    Chan YW, Tan KY, Tan CH
    Toxicon, 2022 Dec;220:106942.
    PMID: 36240856 DOI: 10.1016/j.toxicon.2022.106942
    Snakebite envenoming is an important neglected tropical disease. Antivenom supply, however, remains limited in many parts of the world. This study aimed to examine the protein composition, immunoreactivity and neutralization efficacy of a new antivenom product (VINS Philippine Elapid Antivenoms, VPEAV) developed for the treatment of snakebite envenoming caused by the Philippine Cobra (Naja philippinensis), Samar Cobra (Naja samarensis) and King Cobra (Ophiophagus hannah). Size-exclusion chromatography, sodium-dodecyl sulfate-polyacrylamide gel electrophoresis and tandem mass spectrometry showed that VPEAV consisted of F(ab)'2 (∼90% of total antivenom proteins) with minimal protein impurities. Indirect ELISA showed varying immunoreactivity of VPEAV toward the different venoms (EC50 = 4-16 μg/ml), indicating distinct venom antigenicity between the species. In mice, the neutralization potency of VPEAV against the King Cobra venom was moderate (potency, P = 2.6 mg/ml, defined as the amount of venom completely neutralized per unit volume of antivenom). The potency was significantly lower against the N. philippinensis and N. samarensis venoms (P = 0.18-0.30 mg/ml), implying a higher dose may be needed for effective neutralization of the Naja venoms. Together, the findings suggest the potential and limitation of VPEAV in neutralizing the venom toxicity of the three Philippine elapid snakes.
    Matched MeSH terms: Elapid Venoms/chemistry
  15. Fulltext Malaysian and Chinese King Cobra Venom Cytotoxicity in Melanoma and Neonatal Foreskin Fibroblasts Is Mediated by Age and Geography
    Op den Brouw B, Fernandez-Rojo MA, Charlton T, Fry BG, Ikonomopoulou MP
    Toxins (Basel), 2023 Sep 04;15(9).
    PMID: 37755975 DOI: 10.3390/toxins15090549
    Snake venoms constitute a complex, rapidly evolving trait, whose composition varies between and within populations depending on geographical location, age and preys (diets). These factors have determined the adaptive evolution for predatory success and link venom heterogeneity with prey specificity. Moreover, understanding the evolutionary drivers of animal venoms has streamlined the biodiscovery of venom-derived compounds as drug candidates in biomedicine and biotechnology. The king cobra (Ophiophagus hannah; Cantor, 1836) is distributed in diverse habitats, forming independent populations, which confer differing scale markings, including between hatchlings and adults. Furthermore, king cobra venoms possess unique cytotoxic properties that are used as a defensive trait, but their toxins may also have utility as promising anticancer-agent candidates. However, the impact of geographical distribution and age on these potential venom applications has been typically neglected. In this study, we hypothesised that ontogenetic venom variation accompanies the morphological distinction between hatchlings and adults. We used non-transformed neonatal foreskin (NFF) fibroblasts to examine and compare the variability of venom cytotoxicity between adult captive breeding pairs from Malaysian and Chinese lineages, along with that of their progeny upon hatching. In parallel, we assessed the anticancer potential of these venoms in human-melanoma-patient-derived cells (MM96L). We found that in a geographical distribution and gender-independent manner, venoms from hatchlings were significantly less cytotoxic than those from adults (NFF; ~Log EC50: 0.5-0.6 vs. 0.2-0.35 mg/mL). This is consistent with neonates occupying a semifossorial habitat, while adults inhabit more above-ground habitats and are therefore more conspicuous to potential predators. We also observed that Malaysian venoms exhibited a slightly higher cytotoxicity than those from the Chinese cobra cohorts (NFF; Log EC50: 0.1-0.3 vs. 0.3-0.4 mg/mL), which is consistent with Malaysian king cobras being more strongly aposematically marked. These variations are therefore suggestive of differential anti-predator strategies associated with the occupation of distinct niches. However, all cobra venoms were similarly cytotoxic in both melanoma cells and fibroblasts, limiting their potential medical applications in their native forms.
    Matched MeSH terms: Elapid Venoms*
  16. Fulltext Unveiling the functional epitopes of cobra venom cytotoxin by immunoinformatics and epitope-omic analyses
    Hiu JJ, Fung JKY, Tan HS, Yap MKK
    Sci Rep, 2023 Jul 28;13(1):12271.
    PMID: 37507457 DOI: 10.1038/s41598-023-39222-2
    Approximate 70% of cobra venom is composed of cytotoxin (CTX), which is responsible for the dermonecrotic symptoms of cobra envenomation. However, CTX is generally low in immunogenicity, and the antivenom is ineffective in attenuating its in vivo toxicity. Furthermore, little is known about its epitope properties for empirical antivenom therapy. This study aimed to determine the epitope sequences of CTX using the immunoinformatic analyses and epitope-omics profiling. A conserved CTX was used in this study to determine its T-cell and B-cell epitope sequences using immunoinformatic tools and molecular docking simulation with different Human Leukocyte Antigens (HLAs). The potential T-cell and B-cell epitopes were 'KLVPLFY,' 'CPAGKNLCY,' 'MFMVSTPTK,' and 'DVCPKNSLL.' Molecular docking simulations disclosed that the HLA-B62 supertype exhibited the greatest binding affinity towards cobra venom cytotoxin. The namely L7, G18, K19, N20, M25, K33, V43, C44, K46, N47, and S48 of CTX exhibited prominent intermolecular interactions with HLA-B62. The multi-enzymatic-limited-digestion/liquid chromatography-mass spectrometry (MELD/LC-MS) also revealed three potential epitope sequences as 'LVPLFYK,' 'MFMVS,' and 'TVPVKR'. From different epitope mapping approaches, we concluded four potential epitope sites of CTX as 'KLVPLFYK', 'AGKNL', 'MFMVSTPKVPV' and 'DVCPKNSLL'. Site-directed mutagenesis of these epitopes confirmed their locations at the functional loops of CTX. These epitope sequences are crucial to CTX's structural folding and cytotoxicity. The results concluded the epitopes that resided within the functional loops constituted potential targets to fabricate synthetic epitopes for CTX-targeted antivenom production.
    Matched MeSH terms: Elapid Venoms*
  17. A comparative study of the biological properties of Dendroaspis (mamba) snake venoms
    Tan NH, Arunmozhiarasi A, Ponnudurai G
    Comp Biochem Physiol C Comp Pharmacol Toxicol, 1991;99(3):463-6.
    PMID: 1685421
    1. The biological properties of twelve samples of venoms from all four species of Dendroaspis (mamba) were investigated. 2. Dendroaspis venoms generally exhibited very low levels of protease, phosphodiesterase and alkaline phosphomonoesterase; low to moderately low level of 5'-nucleotidase and very high hyaluronidase activities, but were devoid of L-amino acid oxidase, phospholipase A, acetylcholinesterase and arginine ester hydrolase activities. The unusual feature in venom enzyme content can be used to distinguish Dendroaspis venoms from other snake venoms. 3. All Dendroaspis venoms did not exhibit hemorrhagic or procoagulant activity. Some Dendroaspis venoms, however, exhibited strong anticoagulant activity. The intravenous median lethal dose of the venoms ranged from 0.5 microgram/g mouse to 4.2 micrograms/g mouse. 4. Venom biological activities are not very useful for the differentiation of the Dendroaspis species. The four Dendroaspis venoms, however, can be differentiated by their venom SDS-polyacrylamide gel electrophoretic patterns.
    Matched MeSH terms: Elapid Venoms/metabolism; Elapid Venoms/pharmacology*; Elapid Venoms/toxicity
  18. Comparative venom proteomics of banded krait (Bungarus fasciatus) from five geographical locales: Correlation of venom lethality, immunoreactivity and antivenom neutralization
    Hia YL, Tan KY, Tan CH
    Acta Trop, 2020 Jul;207:105460.
    PMID: 32278639 DOI: 10.1016/j.actatropica.2020.105460
    The banded krait, Bungarus fasciatus is a medically important venomous snake in Asia. The wide distribution of this species in Southeast Asia and southern China indicates potential geographical variation of the venom which may impact the clinical management of snakebite envenomation. This study investigated the intraspecific venom variation of B. fasciatus from five geographical locales through a venom decomplexing proteomic approach, followed by toxinological and immunological studies. The venom proteomes composed of a total of 9 toxin families, comprising 22 to 31 proteoforms at varying abundances. The predominant proteins were phospholipase A2 (including beta-bungarotoxin), Kunitz-type serine protease inhibitor (KSPI) and three-finger toxins (3FTx), which are toxins that cause neurotoxicity and lethality. The venom lethality varied with geographical origins of the snake, with intravenous median lethal doses (LD50) ranging from 0.45-2.55 µg/g in mice. The Thai Bungarus fasciatus monovalent antivenom (BFMAV) demonstrated a dose-dependent increasing immunological binding activity toward all venoms; however, its in vivo neutralization efficacy varied vastly with normalized potency values ranging from 3 to 28 mg/g, presumably due to the compositional differences of dominant proteins in the different venoms. The findings support that antivenom use should be optimized in different geographical areas. The development of a pan-regional antivenom may be a more sustainable solution for the treatment of snakebite envenomation.
    Matched MeSH terms: Elapid Venoms/analysis*; Elapid Venoms/immunology; Elapid Venoms/toxicity
  19. A comparative study on the biological properties of venoms from juvenile and adult common tiger snake (Notechis scutatus) venoms
    Tan NH, Ponnudurai G, Mirtschin PJ
    Comp. Biochem. Physiol., B, 1993 Nov;106(3):651-4.
    PMID: 8281760
    1. The biological properties of venoms from juvenile and adult common tiger snakes (Notechis scutatus) were compared. 2. The lethality, procoagulant activity and enzymatic activities of the juvenile venom were not substantially different from those of the adult venom. 3. Electrophoretic studies, however, indicated some minor differences in the protein composition of the juvenile and adult venoms.
    Matched MeSH terms: Elapid Venoms/analysis*
  20. Fulltext A pan-specific antiserum produced by a novel immunization strategy shows a high spectrum of neutralization against neurotoxic snake venoms
    Ratanabanangkoon K, Tan KY, Pruksaphon K, Klinpayom C, Gutiérrez JM, Quraishi NH, et al.
    Sci Rep, 2020 07 09;10(1):11261.
    PMID: 32647261 DOI: 10.1038/s41598-020-66657-8
    Snakebite envenomation is a neglected tropical disease of high mortality and morbidity largely due to insufficient supply of effective and affordable antivenoms. Snake antivenoms are mostly effective against the venoms used in their production. It is thus crucial that effective and affordable antivenom(s) with wide para-specificity, capable of neutralizing the venoms of a large number of snakes, be produced. Here we studied the pan-specific antiserum prepared previously by a novel immunization strategy involving the exposure of horses to a 'diverse toxin repertoire' consisting of 12 neurotoxic Asian snake toxin fractions/ venoms from six species. This antiserum was previously shown to exhibit wide para-specificity by neutralizing 11 homologous and 16 heterologous venoms from Asia and Africa. We now show that the antiserum can neutralize 9 out of 10 additional neurotoxic venoms. Altogether, 36 snake venoms belonging to 10 genera from 4 continents were neutralized by the antiserum. Toxin profiles previously generated using proteomic techniques of these 36 venoms identified α-neurotoxins, β-neurotoxins, and cytotoxins as predominant toxins presumably neutralized by the antiserum. The bases for the wide para-specificity of the antiserum are discussed. These findings indicate that it is feasible to generate antivenoms of wide para-specificity against elapid neurotoxic venoms from different regions in the world and raises the possibility of a universal neurotoxic antivenom. This should reduce the mortality resulting from neurotoxic snakebite envenomation.
    Matched MeSH terms: Elapid Venoms/chemistry*
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