The myth of cobra venom cytotoxin: More than just direct cytolytic actions

Hiu, Jia Jin; Yap, Michelle Khai Khun

doi:10.1016/j.toxcx.2022.100123

Cited by 7 publications

(3 citation statements)

References 124 publications

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“…The Malayan Blue Coral Snake (Calliophis bivirgata) contains the 3FTx neurotoxin, calliotoxin, which activates the voltage-gated sodium channel, Na v 1.4 (Yang et al 2016). In some cobra venoms, particularly spitting cobras, cytotoxic 3FTxs are thought to be responsible for serious local dermonecrosis (Hiu and Yap 2022;Lin et al 2022).…”

Section: Three-finger Toxins (3ftx)mentioning

confidence: 99%

A current perspective on snake venom composition and constituent protein families

Tasoulis

2022

Arch Toxicol

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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 snake venom composition (179 species-68 species of elapids and 111 species of vipers), the venoms of vipers and elapids contained 42 different protein families, although 18 were only reported in < 5% of snake species. Based on the mean abundance and occurrence of the 42 protein families, they can be classified into 4 dominant, 6 secondary, 14 minor, and 18 rare protein families. The dominant, secondary and minor categories account for 96% on average of a snake's venom composition. The four dominant protein families are: phospholipase A 2 (PLA 2 ), snake venom metalloprotease (SVMP), three-finger toxins (3FTx), and snake venom serine protease (SVSP). The six secondary protein families are: L-amino acid oxidase (LAAO), cysteine-rich secretory protein (CRiSP), C-type lectins (CTL), disintegrins (DIS), kunitz peptides (KUN), and natriuretic peptides (NP). Venom variation occurs at all taxonomic levels, including within populations. The reasons for venom variation are complex, as variation is not always associated with geographical variation in diet. The four dominant protein families appear to be the most important toxin families in human envenomation, being responsible for coagulopathy, neurotoxicity, myotoxicity and cytotoxicity. Proteomic techniques can be used to investigate the toxicological profile of a snake venom and hence identify key protein families for antivenom immunorecognition.

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Section: Three-finger Toxins (3ftx)mentioning

confidence: 99%

A current perspective on snake venom composition and constituent protein families

Tasoulis

2022

Arch Toxicol

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“…Generally, cytotoxin will interact with the cell membrane to dehydrate the membrane surface and destroy the lipid bilayer structure [31], which can form dimers on the surface of the cell membrane, and then form oligomeric complexes [32]. Finally, it would result in the formation of pores in the membrane lipid bilayer, the leakage of cytoplasm, and the breakdown and dissolution of cells [33]. Actually, cytotoxin not only has the activity of dissolving cells, but also can induce apoptosis and further aggravate wound necrosis: for example, CTX1 and CTX2 can induce apoptosis through the lysosomal pathway and the release of cathepsin to the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

Clinical study of anti-snake venom blockade in the treatment of local tissue necrosis caused by Chinese cobra (Naja atra) bites

Zeng

Hou

et al. 2022

PLoS Negl Trop Dis

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Objective This study aimed to evaluate the clinical therapeutic efficacy of anti-snake venom serum blockade in treating local tissue necrosis caused by Chinese cobra (Naja atra) bites. Methods Patients bitten by a Chinese cobra (Naja atra) (n = 50) that met the inclusion criteria were randomly divided into two groups: the experimental group (n = 25) and the control group (n = 25). The experimental group received regular as well as anti-snake venom serum blocking treatment, whereas regular treatment plus chymotrypsin blocking therapy was given to the control group. The necrotic volumes around snake wounds in these groups were detected on the first, third and seventh days. On the third day of treatment, some local tissues in the wounds were randomly selected for pathological biopsy, and the necrosis volume of the local tissue was observed. Furthermore, the amount of time required for wound healing was recorded. Results On the third and seventh days post-treatment, the necrotic volume of the wound of the experimental group was much smaller than that of the control group, and the experimental group’s wound healing time was shorter than that of the control group (all p < 0.05). Moreover, the pathological biopsies taken from the control group showed nuclear pyknosis, fragmentation, sparse nuclear density, and blurred edges, and the degree of necrosis was much higher than that of the experimental group. Conclusions Anti-snake venom blocking therapy is a new and improved therapy with good clinical effect on local tissue necrosis caused by Chinese cobra bites; moreover, it is superior to conventional chymotrypsin blocking therapy in the treatment of cobra bites. It can better neutralize and prevent the spread of the toxin, reduce tissue necrosis, and shorten the course of the disease by promoting healing of the wound. Furthermore, this treatment plan is also applicable to wound necrosis caused by other snake toxins, such as tissue necrosis caused by elapidae and viper families. Clinical Trial Registration This trial is registered in the Chinese Clinical Trial Registry, a primary registry of International Clinical Trial Registry Platform, World Health Organization (Registration No. ChiCTR2200059070; trial URL:http://www.chictr.org.cn/edit.aspx?pid=134353&htm=4).

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“…CTX is a highly basic amphipathic protein containing positively charged groups. This protein has also been shown to be the major toxin component of venom that is responsible for the cytotoxic effects of N. atra venom on cells and tissue [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a Monoclonal scFv against Cytotoxin to Neutralize Cytolytic Activity Induced by Naja atra Venom on Myoblast C2C12 Cells

Liu

Chou

et al. 2022

Toxins

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The Taiwanese cobra, Naja atra, is a clinically significant species of snake observed in the wild in Taiwan. Victims bitten by N. atra usually experience severe pain and local tissue necrosis. Although antivenom is available for treatment of cobra envenomation, its neutralization potency against cobra-induced necrosis is weak, with more than 60% of cobra envenoming patients developing tissue necrosis after antivenom administration. The present study found that cytotoxin (CTX) is a key component of N. atra venom responsible for cytotoxicity against myoblast cells. Anti-CTX IgY was generated in hens, and the spleens of these hens were used to construct libraries for the development of single chain variable fragments (scFv). Two anti-CTX scFv, S1 and 2S7, were selected using phage display technology and biopanning. Both polyclonal IgY and monoclonal scFv S1 reacted specifically with CTX in cobra venom. In a cell model assay, the CTX-induced cytolytic effect was inhibited only by monoclonal scFv S1, not by polyclonal IgY. Moreover, the neutralization potency of scFv S1 was about 3.8 mg/mg, approximately three times higher than that of conventional freeze-dried neurotoxic antivenom (FNAV). Collectively, these results suggest that scFv S1 can effectively neutralize CTX-induced cytotoxicity and, when combined with currently available antivenom, can improve the potency of the latter, thereby preventing tissue damage induced by cobra envenoming.

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The myth of cobra venom cytotoxin: More than just direct cytolytic actions

Cited by 7 publications

References 124 publications

A current perspective on snake venom composition and constituent protein families

A current perspective on snake venom composition and constituent protein families

Clinical study of anti-snake venom blockade in the treatment of local tissue necrosis caused by Chinese cobra (Naja atra) bites

Development of a Monoclonal scFv against Cytotoxin to Neutralize Cytolytic Activity Induced by Naja atra Venom on Myoblast C2C12 Cells

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