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12 pages, 300 KiB

Open AccessArticle

A Retrospective Cohort Study of Cobra Envenomation: Clinical Characteristics, Treatments, and Outcomes

by Phantakan Tansuwannarat, Achara Tongpoo, Suraphong Phongsawad, Charuwan Sriapha, Winai Wananukul and Satariya Trakulsrichai

Toxins 2023, 15(7), 468; https://doi.org/10.3390/toxins15070468 - 20 Jul 2023

Cited by 8 | Viewed by 3016

Abstract

This study investigated the clinical characteristics, treatments, and outcomes of envenomation involving cobra species in Thailand (Naja kaouthia, Naja siamensis, and Naja sumatrana). Data of patients who had been bitten by a cobra or inoculated via the eyes/skin in [...] Read more.

This study investigated the clinical characteristics, treatments, and outcomes of envenomation involving cobra species in Thailand (Naja kaouthia, Naja siamensis, and Naja sumatrana). Data of patients who had been bitten by a cobra or inoculated via the eyes/skin in 2018–2021 were obtained from the Ramathibodi Poison Center. There were 1045 patients admitted during the 4-year study period (bite, n = 539; ocular/dermal inoculation, n = 506). Almost all patients with ocular/dermal inoculation had eye involvement and ocular injuries, but none had neurological effects. Most of the patients bitten by a cobra had local effects (69.0%) and neurological signs and symptoms (55.7%). The median interval between the bite and the onset of neurological symptoms was 1 h (range, 10 min to 24 h). Accordingly, patients should be observed closely in hospitals for at least 24 h after a bite. Intubation with ventilator support was required in 45.5% of patients and for a median duration of 1.1 days. Antivenom was administered in 63.5% of cases. There were nine deaths, most of which resulted from severe infection. Neurological effects and intubation were significantly more common after a monocled cobra bite than after a spitting cobra bite. The administration of antivenom with good supportive care, including the appropriate management of complications, especially wound infection, might decrease fatality. Full article

(This article belongs to the Section Animal Venoms)

31 pages, 5632 KiB

Open AccessArticle

Description of a New Cobra (Naja Laurenti, 1768; Squamata, Elapidae) from China with Designation of a Neotype for Naja atra

by Sheng-Chao Shi, Gernot Vogel, Li Ding, Ding-Qi Rao, Shuo Liu, Liang Zhang, Zheng-Jun Wu and Ze-Ning Chen

Animals 2022, 12(24), 3481; https://doi.org/10.3390/ani12243481 - 9 Dec 2022

Cited by 12 | Viewed by 14632

Abstract

Taxonomic frameworks for medically important species such as cobras (genus Naja Laurenti, 1768; Squamata, Elapidae) are essential for the medical treatment of snake bites and accurate antivenin development. In this paper, we described the former N. kaouthia populations recorded from China as a [...] Read more.

Taxonomic frameworks for medically important species such as cobras (genus Naja Laurenti, 1768; Squamata, Elapidae) are essential for the medical treatment of snake bites and accurate antivenin development. In this paper, we described the former N. kaouthia populations recorded from China as a new species and designated a neotype for N. atra-based morphological and mitochondrial phylogenetic analysis. The new species N. fuxisp. nov. was morphologically diagnosed from N. kaouthia by (1) regular single narrow crossband present on the middle and posterior parts of the dorsum (3–15, 7.9 ± 2.7, n = 32) and the dorsal surface of the tail (1–6, 4.2 ± 1.1, n = 32) of both adults and juveniles, buff-colored with dark fringes on both edges, vs. South Asian populations (n = 39) and Southeast Asian populations (n = 35) without cross bands, with irregular cross bands or multiple light-colored crossbands pairs, or densely woven lines; (2) small scales between the posterior chin shields, usually three (40%) or two (37%), rarely four (13%), or one (10%) (n = 30) vs. mostly one (81%) and rarely two (19%) (n = 28); (3) ventrals 179–205 (195.4 ± 6.7, n = 33) vs. South Asian populations 179–199 (188.7 ± 5.9, n = 12); Southeast Asian populations 168–186 (177.8 ± 4.9, n = 18). Phylogenetically, the new species forms an independent sister clade to the clade including N. atra, N. kaouthia, N. oxiana and N. sagittifera. Furthermore, the subspecies N. naja polyocellata should be resurrected and recognized as a full species, N. polyocellatacomb. nov., and the subspecies N. sumatrana miolepis should be resurrected. Full article

(This article belongs to the Special Issue Evolution, Diversity, and Conservation of Herpetofauna)

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17 pages, 3256 KiB

Open AccessArticle

Equatorial Spitting Cobra (Naja sumatrana) from Malaysia (Negeri Sembilan and Penang), Southern Thailand, and Sumatra: Comparative Venom Proteomics, Immunoreactivity and Cross-Neutralization by Antivenom

by Choo Hock Tan, Kae Yi Tan, Kin Ying Wong, Nget Hong Tan and Ho Phin Chong

Toxins 2022, 14(8), 522; https://doi.org/10.3390/toxins14080522 - 29 Jul 2022

Cited by 13 | Viewed by 5024

Abstract

The Equatorial Spitting Cobra (Naja sumatrana) is a medically important venomous snake species in Southeast Asia. Its wide geographical distribution implies potential intra-specific venom variation, while there is no species-specific antivenom available to treat its envenoming. Applying a protein-decomplexing proteomic approach, [...] Read more.

The Equatorial Spitting Cobra (Naja sumatrana) is a medically important venomous snake species in Southeast Asia. Its wide geographical distribution implies potential intra-specific venom variation, while there is no species-specific antivenom available to treat its envenoming. Applying a protein-decomplexing proteomic approach, the study showed that three-finger toxins (3FTX), followed by phospholipases A₂ (PLA₂), were the major proteins well-conserved across N. sumatrana venoms of different locales. Variations were noted in the subtypes and relative abundances of venom proteins. Of note, alpha-neurotoxins (belonging to 3FTX) are the least in the Penang specimen (Ns-PG, 5.41% of total venom proteins), compared with geographical specimens from Negeri Sembilan (Ns-NS, 14.84%), southern Thailand (Ns-TH, 16.05%) and Sumatra (Ns-SU, 10.81%). The alpha-neurotoxin abundance, in general, correlates with the venom’s lethal potency. The Thai Naja kaouthia Monovalent Antivenom (NkMAV) was found to be immunoreactive toward the N. sumatrana venoms and is capable of cross-neutralizing N. sumatrana venom lethality to varying degrees (potency = 0.49–0.92 mg/mL, interpreted as the amount of venom completely neutralized per milliliter of antivenom). The potency was lowest against NS-SU venom, implying variable antigenicity of its lethal alpha-neurotoxins. Together, the findings suggest the para-specific and geographical utility of NkMAV as treatment for N. sumatrana envenoming in Southeast Asia. Full article

(This article belongs to the Special Issue Snakebite and Clinical Toxinology)

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17 pages, 5314 KiB

Open AccessArticle

Cytotoxicity of Venoms and Cytotoxins from Asiatic Cobras (Naja kaouthia, Naja sumatrana, Naja atra) and Neutralization by Antivenoms from Thailand, Vietnam, and Taiwan

by Ho Phin Chong, Kae Yi Tan, Bing-Sin Liu, Wang-Chou Sung and Choo Hock Tan

Toxins 2022, 14(5), 334; https://doi.org/10.3390/toxins14050334 - 10 May 2022

Cited by 17 | Viewed by 4544

Abstract

Envenoming by cobras (Naja spp.) often results in extensive local tissue necrosis when optimal treatment with antivenom is not available. This study investigated the cytotoxicity of venoms and purified cytotoxins from the Monocled Cobra (Naja kaouthia), Taiwan Cobra (Naja [...] Read more.

Envenoming by cobras (Naja spp.) often results in extensive local tissue necrosis when optimal treatment with antivenom is not available. This study investigated the cytotoxicity of venoms and purified cytotoxins from the Monocled Cobra (Naja kaouthia), Taiwan Cobra (Naja atra), and Equatorial Spitting Cobra (Naja sumatrana) in a mouse fibroblast cell line, followed by neutralization of the cytotoxicity by three regional antivenoms: the Thai Naja kaouthia monovalent antivenom (NkMAV), Vietnamese snake antivenom (SAV) and Taiwanese Neuro bivalent antivenom (NBAV). The cytotoxins of N. atra (NA-CTX) and N. sumatrana (NS-CTX) were identified as P-type cytotoxins, whereas that of N. kaouthia (NK-CTX) is S-type. All venoms and purified cytotoxins demonstrated varying concentration-dependent cytotoxicity in the following trend: highest for N. atra, followed by N. sumatrana and N. kaouthia. The antivenoms moderately neutralized the cytotoxicity of N. kaouthia venom but were weak against N. atra and N. sumatrana venom cytotoxicity. The neutralization potencies of the antivenoms against the cytotoxins were varied and generally low across NA-CTX, NS-CTX, and NK-CTX, possibly attributed to limited antigenicity of CTXs and/or different formulation of antivenom products. The study underscores the need for antivenom improvement and/or new therapies in treating local tissue toxicity caused by cobra envenomings. Full article

(This article belongs to the Section Animal Venoms)

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17 pages, 3354 KiB

Open AccessArticle

Isolation and Characterization of A2-EPTX-Nsm1a, a Secretory Phospholipase A₂ from Malaysian Spitting Cobra (Naja sumatrana) Venom

by Nur Atiqah Haizum Abdullah, Muhamad Rusdi Ahmad Rusmili, Syafiq Asnawi Zainal Abidin, Mohd Farooq Shaikh, Wayne C. Hodgson and Iekhsan Othman

Toxins 2021, 13(12), 859; https://doi.org/10.3390/toxins13120859 - 2 Dec 2021

Cited by 6 | Viewed by 4015

Abstract

Phospholipase A₂ (PLA₂) toxins are one of the main toxin families found in snake venom. PLA₂ toxins are associated with various detrimental effects, including neurotoxicity, myotoxicity, hemostatic disturbances, nephrotoxicity, edema, and inflammation. Although Naja sumatrana venom contains substantial quantities [...] Read more.

Phospholipase A₂ (PLA₂) toxins are one of the main toxin families found in snake venom. PLA₂ toxins are associated with various detrimental effects, including neurotoxicity, myotoxicity, hemostatic disturbances, nephrotoxicity, edema, and inflammation. Although Naja sumatrana venom contains substantial quantities of PLA₂ components_, there is limited information on the function and activities of PLA₂ toxins from the venom. In this study, a secretory PLA₂ from the venom of Malaysian N. sumatrana, subsequently named A2-EPTX-Nsm1a, was isolated, purified, and characterized. A2-EPTX-Nsm1a was purified using a mass spectrometry-guided approach and multiple chromatography steps. Based on LC-MSMS, A2-EPTX-Nsm1a was found to show high sequence similarity with PLA₂ from venoms of other Naja species. The PLA₂ activity of A2-EPTX-Nsm1 was inhibited by 4-BPB and EDTA. A2-EPTX-Nsm1a was significantly less cytotoxic in a neuroblastoma cell line (SH-SY5Y) compared to crude venom and did not show a concentration-dependent cytotoxic activity. To our knowledge, this is the first study that characterizes and investigates the cytotoxicity of an Asp49 PLA₂ isolated from Malaysian N. sumatrana venom in a human neuroblastoma cell line. Full article

(This article belongs to the Special Issue Venom-Induced Tissue Damage)

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12 pages, 4915 KiB

Open AccessArticle

Screening Snake Venoms for Toxicity to Tetrahymena Pyriformis Revealed Anti-Protozoan Activity of Cobra Cytotoxins

by Olga N. Kuleshina, Elena V. Kruykova, Elena G. Cheremnykh, Leonid V. Kozlov, Tatyana V. Andreeva, Vladislav G. Starkov, Alexey V. Osipov, Rustam H. Ziganshin, Victor I. Tsetlin and Yuri N. Utkin

Toxins 2020, 12(5), 325; https://doi.org/10.3390/toxins12050325 - 15 May 2020

Cited by 9 | Viewed by 5226

Abstract

Snake venoms possess lethal activities against different organisms, ranging from bacteria to higher vertebrates. Several venoms were shown to be active against protozoa, however, data about the anti-protozoan activity of cobra and viper venoms are very scarce. We tested the effects of venoms [...] Read more.

Snake venoms possess lethal activities against different organisms, ranging from bacteria to higher vertebrates. Several venoms were shown to be active against protozoa, however, data about the anti-protozoan activity of cobra and viper venoms are very scarce. We tested the effects of venoms from several snake species on the ciliate Tetrahymena pyriformis. The venoms tested induced T. pyriformis immobilization, followed by death, the most pronounced effect being observed for cobra Naja sumatrana venom. The active polypeptides were isolated from this venom by a combination of gel-filtration, ion exchange and reversed-phase HPLC and analyzed by mass spectrometry. It was found that these were cytotoxins of the three-finger toxin family. The cytotoxins from several cobra species were tested and manifested toxicity for infusorians. Light microscopy revealed that, because of the cytotoxin action, the infusorians’ morphology was changed greatly, from teardrop-like to an almost spherical shape, this alteration being accompanied by a leakage of cell contents. Fluorescence microscopy showed that the fluorescently labelled cytotoxin 2 from cobra N. oxiana was localized mainly at the membrane of killed infusorians, indicating that cytotoxins may kill T. pyriformis by causing membrane rupture. This work is the first evidence of the antiprotozoal activity of cobra venom cytotoxins, as demonstrated by the example of the ciliate T. pyriformis. Full article

(This article belongs to the Special Issue Animal Venoms and Their Components: Molecular Mechanisms of Action)

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12 pages, 2140 KiB

Open AccessEditor’s ChoiceCommunication

Distinctive Distribution of Secretory Phospholipases A₂ in the Venoms of Afro-Asian Cobras (Subgenus: Naja, Afronaja, Boulengerina and Uraeus)

by Choo Hock Tan, Kin Ying Wong, Nget Hong Tan, Tzu Shan Ng and Kae Yi Tan

Toxins 2019, 11(2), 116; https://doi.org/10.3390/toxins11020116 - 14 Feb 2019

Cited by 28 | Viewed by 5418

Abstract

The protein abundances of phospholipases A₂ in cobra venom proteomes appear to vary among cobra species. To determine the unique distribution of snake venom phospholipases A₂ (svPLA₂) in the cobras, the svPLA₂ activities for 15 cobra species were [...] Read more.

The protein abundances of phospholipases A₂ in cobra venom proteomes appear to vary among cobra species. To determine the unique distribution of snake venom phospholipases A₂ (svPLA₂) in the cobras, the svPLA₂ activities for 15 cobra species were examined with an acidimetric and a colorimetric assay, using egg yolk suspension and 4-nitro-3-octanoyloxy benzoic acid (NOBA) as the substrate. The colorimetric assay showed significant correlation between svPLA₂ enzymatic activities with the svPLA₂ protein abundances in venoms. High svPLA₂ activities were observed in the venoms of Asiatic spitting cobras (Naja sputatrix, Naja sumatrana) and moderate activities in Asiatic non-spitters (Naja naja, Naja atra, Naja kaouthia), African spitters (subgenus Afronaja), and forest cobra (subgenus Boulengerina). African non-spitting cobras of subgenus Uraeus (Naja haje, Naja annulifera, Naja nivea, Naja senegalensis) showed exceptionally low svPLA₂ enzymatic activities. The negligible PLA₂ activity in Uraeus cobra venoms implies that PLA₂ may not be ubiquitous in all snake venoms. The svPLA₂ in cobra envenoming varies depending on the cobra species. This may potentially influence the efficacy of cobra antivenom in specific use for venom neutralization. Full article

(This article belongs to the Section Animal Venoms)

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21 pages, 6463 KiB

Open AccessEditor’s ChoiceArticle

Exploring the Diversity and Novelty of Toxin Genes in Naja sumatrana, the Equatorial Spitting Cobra from Malaysia through De Novo Venom-Gland Transcriptomics

by Ho Phin Chong, Kae Yi Tan, Nget Hong Tan and Choo Hock Tan

Toxins 2019, 11(2), 104; https://doi.org/10.3390/toxins11020104 - 11 Feb 2019

Cited by 29 | Viewed by 6752

Abstract

The equatorial spitting cobra, Naja sumatrana, is a distinct species of medically important venomous snakes, listed as WHO Category 1 in Southeast Asia. The diversity of its venom genes has not been comprehensively examined, although a few toxin sequences annotated to Naja [...] Read more.

The equatorial spitting cobra, Naja sumatrana, is a distinct species of medically important venomous snakes, listed as WHO Category 1 in Southeast Asia. The diversity of its venom genes has not been comprehensively examined, although a few toxin sequences annotated to Naja sputatrix were reported previously through cloning studies. To investigate this species venom genes’ diversity, de novo venom-gland transcriptomics of N. sumatrana from West Malaysia was conducted using next-generation sequencing technology. Genes encoding toxins represented only 60 of the 55,396 transcripts, but were highly expressed, contributing to 79.22% of total gene expression (by total FPKM) in the venom-glands. The toxin transcripts belong to 21 families, and 29 transcripts were further identified as full-length. Three-finger toxins (3FTx) composed of long, short, and non-conventional groups, constituted the majority of toxin transcripts (91.11% of total toxin FPKM), followed by phospholipase A₂ (PLA₂, 7.42%)—which are putatively pro-inflammatory and cytotoxic. The remaining transcripts in the 19 families were expressed at extremely low levels. Presumably, these toxins were associated with ancillary functions. Our findings unveil the diverse toxin genes unique to N. sumatrana, and provide insights into the pathophysiology of N. sumatrana envenoming. Full article

(This article belongs to the Section Animal Venoms)

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12 pages, 597 KiB

Open AccessReview

Malaysian Cobra Venom: A Potential Source of Anti-Cancer Therapeutic Agents

by Syafiq Asnawi Zainal Abidin, Yee Qian Lee, Iekhsan Othman and Rakesh Naidu

Toxins 2019, 11(2), 75; https://doi.org/10.3390/toxins11020075 - 1 Feb 2019

Cited by 23 | Viewed by 8769

Abstract

Cancer is a deadly disease and there is an urgent need for the development of effective and safe therapeutic agents to treat it. Snake venom is a complex mixture of bioactive proteins that represents an attractive source of novel and naturally-derived anticancer agents. [...] Read more.

Cancer is a deadly disease and there is an urgent need for the development of effective and safe therapeutic agents to treat it. Snake venom is a complex mixture of bioactive proteins that represents an attractive source of novel and naturally-derived anticancer agents. Malaysia is one of the world’s most biodiverse countries and is home to various venomous snake species, including cobras. Naja kaouthia, Naja sumatrana, and Ophiophagus hannah are three of the most common cobra species in Malaysia and are of medical importance. Over the past decades, snake venom has been identified as a potential source of therapeutic agents, including anti-cancer agents. This present review highlights the potential anticancer activity of the venom and purified venom protein of N. kaouthia, N. sumatrana, and O. hannah. In conclusion, this review highlights the important role of the venom from Malaysian cobras as an important resource that researchers can exploit to further investigate its potential in cancer treatment. Full article

(This article belongs to the Special Issue Venom and Toxin as Targeted Therapy)

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