Snake venom proteome and immuno-profiling of the hundred-pace viper, Deinagkistrodon acutus, in Taiwan

Chen, Po-Chuan; Huang, Ming-Nan; Chang, Jia‐Feng; Liu, Chien-Chun; Chen, Chun-Kuei; Hsieh, Chu‐Chin

doi:10.1016/j.actatropica.2018.09.017

Cited by 30 publications

(23 citation statements)

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“…There were two PLA 2 (~5% of total venom proteins) detected in T. nebularis venom proteome. The low abundance of PLA 2 is similar to that reported in the venom proteomes of C. rhodostoma and D. acutus (<10%) [29,35] but differs markedly from that reported for the arboreal T. stejnegeri (~20%), P. mucrosquamatus (~25%) [23], P. flavoviridis (~55%) [13] and T. purpureomaculatus (33.01%) [27]. One of the PLA 2 proteoforms identified in T. nebularis venom proteome is homologous to the Lys-49 basic PLA 2 of P. mucrosquamatus (P22640) known for edema-inducing property [43], supporting the inflammatory feature of progressive painful edema in local envenoming by the pit viper.…”

Section: Resultssupporting

confidence: 79%

“…com.). On a side note, thrombocytopenia is also a common clinical feature of Malayan pit viper ( C. rhodostoma ) and hundred-pace pit viper ( Deinagkistrodon acutus ) envenomings and the effect has been correlated to the abundant snaclecs or C-type lectins found in the venoms (20–40%) [29,35]. In contrast, T. stejnegeri and Protobothrops mucrosquamatus envenomings rarely cause thrombocytopenia [36] and this has been attributed to the low abundance of C-type lectins in T. stejnegeri and P. mucrosquamatus venoms (1.5% and 3.9%, respectively) [23].…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, T. stejnegeri and Protobothrops mucrosquamatus envenomings rarely cause thrombocytopenia [36] and this has been attributed to the low abundance of C-type lectins in T. stejnegeri and P. mucrosquamatus venoms (1.5% and 3.9%, respectively) [23]. The composition difference of snaclec proteins among different pit viper venoms provides a scientific basis for distinguishing thrombocytopenic D. acutus bite from the hemorrhagic T. stejnegeri and P. mucrosquamatus bites by clinicians in Taiwan [35,36]. Nonetheless, in many Southeast Asian countries including Malaysia, this syndromic divergence is not clear-cut and non-specific, as many Trimeresurus sp.…”

Section: Resultsmentioning

confidence: 99%

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

Tan

et al. 2019

Toxins

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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.

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Section: Resultssupporting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Tan

et al. 2019

Toxins

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“…For protein identification, the proteins in each fraction were subjected to tryptic digestion before liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, as described previously [20]. Briefly, 1 μg of protein was reduced by incubation with 10 mM dithiothreitol (DTT) at 60˚C for one hour and alkylated by incubation with 30 mM iodoacetamide (IAM) at room temperature in the dark for 30 minutes.…”

Section: In-solution Tryptic Digestion Of Proteinmentioning

confidence: 99%

Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models

et al. 2020

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Naja atra envenomation is one of the most significant clinical snakebite concerns in Taiwan. Taiwanese freeze-dried neurotoxic antivenom (FNAV) is currently used clinically for the treatment of cobra snakebite, and has been shown to limit the mortality of cobra envenomation to less than 1%. However, more than half of victims (60%) require surgery because of local tissue necrosis, a major problem in patients with cobra envenomation. Although the importance of evaluating the neutralizing effect of FNAV on this pathology is recognized, whether FNAV is able to prevent the local necrosis extension induced by N. atra venom has not been investigated in detail. Cytotoxins (CTXs) are considered as the major components of N. atra venom that cause necrosis. In the current study, we isolated CTXs from whole cobra venom and used both whole venom and purified CTXs to develop animal models for assessing the neutralization potential of FNAV against venom necrotizing activity. Local necrotic lesions were successfully produced in mice using CTXs in place of whole N. atra venom. FNAV was able to rescue mice from a subcutaneously injected lethal dose of cobra venom; however, it was unable to prevent CTX-induced dermo-necrosis. Furthermore, using the minimal necrosis dose (MND) of CTXs and venom proteome data, we found a dose of whole N. atra venom suitable for FNAV and developed a workable protocol for inducing local necrosis in rodent models that successfully imitated the clinical circumstance of cobra envenoming. This information provides a more comprehensive understanding of PLOS Neglected Tropical Diseases | https://doi.the pathophysiology of N. atra envenomation, and serves as a guide for improving current antivenom strategies and advancing clinical snakebite management in Taiwan. Author summaryNaja atra envenomation is an important public health issue in Taiwan. Although the mortality rate of cobra snakebite is controlled using antivenom, more than half of victims develop symptoms of local necrosis and require surgical intervention. Whether the Taiwanese freeze-dried neurotoxic antivenom (FNAV) currently in clinical use is able to prevent the local necrosis extension induced by N. atra venom is still unclear. In this study, we developed a dermo-necrosis animal model using purified cytotoxins (CTXs), the major necrosis-related proteins from N. atra venom. We found that FNAV was able to neutralize the lethality of whole cobra venom, but was unable to neutralize the necrosis induced by CTXs in vivo. This finding introduced an example that supplementary quality control assays may be necessary to determine the effectiveness of antivenoms in neutralizing specific pathology induced by the venom; only evaluating the rodent lethality prevention is insufficient. Our results provide insights that should help improve current antivenoms and advance cobra snakebite management in Taiwan.Pathogenesis of local necrosis induced by Naja atra venom PLOS Neglected Tropical Diseases | https://doi.org/10.The lyophilized fractions from RP-HPLC were d...

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“…De. acutus (Hundred-Pace snake) is mostly distributed in Eastern and Southern Taiwan and primarily inhabits medium altitude mountains and forests [7,8]. T. mucrosquamatus (Taiwan Habu) is widely distributed in low-to-medium altitude areas in Taiwan [9].…”

Section: Introductionmentioning

confidence: 99%

Effect of Traditional Chinese Medicine on Long-Term Outcomes of Snakebite in Taiwan

Huang

Hsieh

2020

Toxins

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Herein, we review the characteristics of the six predominant venomous snakes in Taiwan and the effects of traditional Chinese medicine on the long-term outcomes of snakebite venom. We electronically searched databases, including PubMed, ClinicalKey, China National Knowledge Infrastructure, National Digital Library of Theses and Dissertations in Taiwan, and Airiti Library, from their inception to November 2019 by using the following Medical Subject Headings’ keywords: snakebite, long-term, chronic, Chinese medicine, CAM, herb, and Taiwan. The most common long-term effects of snakebite envenomation include “migraine-like syndrome”, brain injuries caused by hypoxia or intracranial hemorrhage, and chronic kidney disease. In addition, hypopituitarism is also worth mentioning. Traditional Chinese medicine can potentially be used in a complementary or alternative treatment for these effects, but additional studies are needed.

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Snake venom proteome and immuno-profiling of the hundred-pace viper, Deinagkistrodon acutus, in Taiwan

Cited by 30 publications

References 68 publications

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

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

Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models

Effect of Traditional Chinese Medicine on Long-Term Outcomes of Snakebite in Taiwan

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