Toxinology of Snake Venoms: The Malaysian Context

Tan, Choo Hock; Tan, Nget Hong

doi:10.1007/978-94-007-6410-1_13

Cited by 3 publications

(4 citation statements)

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“…Three-finger toxins typically constitute the main bulk of toxins in elapid venoms, in particular venoms of the cobras, king cobra and some sea snakes (Tan et al, 2015b; Tan & Tan, 2015). The mini-proteins fold in a similar pattern, with three β-stranded loops extending from a central core containing four to five conserved disulphide bridges (Hedge et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

“…In Southeast Asia, cobra ( Naja sp.) is a common cause of snakebites with life-threatening outcomes: cobras are capable of injecting large amount of venom and the venom generally contains potent neurotoxins that can paralyse the envenomed subjects in minutes (Tan & Tan, 2015). Listed under category I of medically important venomous snakes (Chippaux, 2010), the monocled cobra ( Naja kaouthia ) is a widespread species found across the Eastern Indian subcontinent to most parts of Indochina (including the Peninsular Malaya) and the southern part of China.…”

Section: Introductionmentioning

confidence: 99%

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Comparative venom gland transcriptomics ofNaja kaouthia(monocled cobra) from Malaysia and Thailand: elucidating geographical venom variation and insights into sequence novelty

Tan

Chanhome

et al. 2017

PeerJ

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BackgroundThe monocled cobra (Naja kaouthia) is a medically important venomous snake in Southeast Asia. Its venom has been shown to vary geographically in relation to venom composition and neurotoxic activity, indicating vast diversity of the toxin genes within the species. To investigate the polygenic trait of the venom and its locale-specific variation, we profiled and compared the venom gland transcriptomes of N. kaouthia from Malaysia (NK-M) and Thailand (NK-T) applying next-generation sequencing (NGS) technology.MethodsThe transcriptomes were sequenced on the Illumina HiSeq platform, assembled and followed by transcript clustering and annotations for gene expression and function. Pairwise or multiple sequence alignments were conducted on the toxin genes expressed. Substitution rates were studied for the major toxins co-expressed in NK-M and NK-T.Results and discussionThe toxin transcripts showed high redundancy (41–82% of the total mRNA expression) and comprised 23 gene families expressed in NK-M and NK-T, respectively (22 gene families were co-expressed). Among the venom genes, three-finger toxins (3FTxs) predominated in the expression, with multiple sequences noted. Comparative analysis and selection study revealed that 3FTxs are genetically conserved between the geographical specimens whilst demonstrating distinct differential expression patterns, implying gene up-regulation for selected principal toxins, or alternatively, enhanced transcript degradation or lack of transcription of certain traits. One of the striking features that elucidates the inter-geographical venom variation is the up-regulation of α-neurotoxins (constitutes ∼80.0% of toxin’s fragments per kilobase of exon model per million mapped reads (FPKM)), particularly the long-chain α-elapitoxin-Nk2a (48.3%) in NK-T but only 1.7% was noted in NK-M. Instead, short neurotoxin isoforms were up-regulated in NK-M (46.4%). Another distinct transcriptional pattern observed is the exclusively and abundantly expressed cytotoxin CTX-3 in NK-T. The findings suggested correlation with the geographical variation in proteome and toxicity of the venom, and support the call for optimising antivenom production and use in the region. Besides, the current study uncovered full and partial sequences of numerous toxin genes from N. kaouthia which have not been reported hitherto; these include N. kaouthia-specific l-amino acid oxidase (LAAO), snake venom serine protease (SVSP), cystatin, acetylcholinesterase (AChE), hyaluronidase (HYA), waprin, phospholipase B (PLB), aminopeptidase (AP), neprilysin, etc. Taken together, the findings further enrich the snake toxin database and provide deeper insights into the genetic diversity of cobra venom toxins.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparative venom gland transcriptomics ofNaja kaouthia(monocled cobra) from Malaysia and Thailand: elucidating geographical venom variation and insights into sequence novelty

Tan

Chanhome

et al. 2017

PeerJ

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“…comprise of two important toxin families: three-finger toxins (3FTx) and PLA 2 . 28,29 Within the 3FTx family, there are at least two toxin types with different tissue targets and toxic activities, that is, the SNTX and LNTXs, which block postsynaptic nicotinic receptors, and CTX (also known as cardiotoxins), which exhibit cytolytic activity. Earlier, compositional variations of cobra venoms have been reported and attributed to factors such as differences in the biogeographical distribution of the species.…”

Section: Discussionmentioning

confidence: 99%

Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan: Insights into Toxicity and Antivenom Neutralization

Wong¹,

Tan²,

Tan³

2016

The American Society of Tropical Medicine and Hygiene

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Abstract. 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). Cationexchange 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 A 2 (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.

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“…Another study carried out at Malaysia for the determination of LD 50 of crude venom of Bungarus candidus depicts the variation in the lethality of venom with an I.V. LD 50 of 0.11 μg/g [20].…”

Section: Resultsmentioning

confidence: 99%

Determination of Lethal Dose (LD50) of Venom of four Different Poisonous Snakes found in Pakistan

Parveen¹,

M²,

Ali³

et al. 2017

Biochem Mol biol J

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Toxinology of Snake Venoms: The Malaysian Context

Cited by 3 publications

References 178 publications

Comparative venom gland transcriptomics ofNaja kaouthia(monocled cobra) from Malaysia and Thailand: elucidating geographical venom variation and insights into sequence novelty

Comparative venom gland transcriptomics ofNaja kaouthia(monocled cobra) from Malaysia and Thailand: elucidating geographical venom variation and insights into sequence novelty

Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan: Insights into Toxicity and Antivenom Neutralization

Determination of Lethal Dose (LD50) of Venom of four Different Poisonous Snakes found in Pakistan

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