Snake Venom Protease Inhibitors: Enhanced Identification, Expanding Biological Function, and Promising Future

Inagaki, Hidetoshi

doi:10.1007/978-94-007-6410-1_16

Cited by 7 publications

(11 citation statements)

References 102 publications

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“…Snake venom protease inhibitors primarily disrupt blood coagulation resulting in blood loss and the death of preys [ 42 ]. The largest and most widely distributed family is Kunitz-type protein inhibitors, which strongly inhibit serine proteases.…”

Section: Discussionmentioning

confidence: 99%

Exploring Toxin Genes of Myanmar Russell’s Viper, Daboia siamensis, through De Novo Venom Gland Transcriptomics

Yee

Macrander

Vasieva

et al. 2023

Toxins

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The Russell’s viper (Daboia siamensis) is a medically important venomous snake in Myanmar. Next-generation sequencing (NGS) shows potential to investigate the venom complexity, giving deeper insights into snakebite pathogenesis and possible drug discoveries. mRNA from venom gland tissue was extracted and sequenced on the Illumina HiSeq platform and de novo assembled by Trinity. The candidate toxin genes were identified via the Venomix pipeline. Protein sequences of identified toxin candidates were compared with the previously described venom proteins using Clustal Omega to assess the positional homology among candidates. Candidate venom transcripts were classified into 23 toxin gene families including 53 unique full-length transcripts. C-type lectins (CTLs) were the most highly expressed, followed by Kunitz-type serine protease inhibitors, disintegrins and Bradykinin potentiating peptide/C-type natriuretic peptide (BPP-CNP) precursors. Phospholipase A2, snake venom serine proteases, metalloproteinases, vascular endothelial growth factors, L-amino acid oxidases and cysteine-rich secretory proteins were under-represented within the transcriptomes. Several isoforms of transcripts which had not been previously reported in this species were discovered and described. Myanmar Russell’s viper venom glands displayed unique sex-specific transcriptome profiles which were correlated with clinical manifestation of envenoming. Our results show that NGS is a useful tool to comprehensively examine understudied venomous snakes.

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Section: Discussionmentioning

confidence: 99%

Exploring Toxin Genes of Myanmar Russell’s Viper, Daboia siamensis, through De Novo Venom Gland Transcriptomics

Yee

Macrander

Vasieva

et al. 2023

Toxins

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“…Snake venom is a highly variable mixture of dozens of enzymatic and non-enzymatic proteins which may produce a range of local and systemic effects in bite victims, with some being life-threatening while others being permanently debilitating [ 1 , 6 ]. The clinical effects of snakebite envenoming can be divided into three main pathologies: haemotoxicity, neurotoxicity and tissue damaging effects [ 1 , 7 , 8 ]. Although most life-threatening pathologies in snake bite victims result from the haemotoxic and neurotoxic effects, the tissue damaging activities are the main cause of life-long disabilities such as blindness and amputations [ 1 – 3 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although annual morbidity rates surpass 450,000 individuals, most research has been focusing on the haemotoxic and neurotoxic effects and considerably less on venom-induced tissue damage [ 1 , 10 ]. The cell- and tissue damaging effects of snake venoms may result in a range of pathologies including (local) haemorrhage, muscle and skin necrosis, oedema and organ failure [ 1 , 8 , 11 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a high-throughput in vitro screening method for the assessment of cell-damaging activities of snake venoms

Bittenbinder,

Capinha,

Da Costa Pereira

et al. 2023

PLoS Negl Trop Dis

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Snakebite envenoming is a globally important public health issue that has devastating consequences on human health and well-being, with annual mortality rates between 81,000 and 138,000. Snake venoms may cause different pathological effects by altering normal physiological processes such as nervous transfer and blood coagulation. In addition, snake venoms can cause severe (local) tissue damage that may result in life-long morbidities, with current estimates pointing towards an additional 450,000 individuals that suffer from permanent disabilities such as amputations, contractions and blindness. Despite such high morbidity rates, research to date has been mainly focusing on neurotoxic and haemotoxic effects of snake venoms and considerably less on venom-induced tissue damage. The molecular mechanisms underlaying this pathology include membrane disruption and extracellular matrix degradation. This research describes methods used to study the (molecular) mechanisms underlaying venom-induced cell- and tissue damage. A selection of cellular bioassays and fluorescent microscopy were used to study cell-damaging activities of snake venoms in multi-well plates, using both crude and fractionated venoms. A panel of 10 representative medically relevant snake species was used, which cover a large part of the geographical regions most heavily affected by snakebite. The study comprises both morphological data as well as quantitative data on cell metabolism and viability, which were measured over time. Based on this data, a distinction could be made in the ways by which viper and elapid venoms exert their effects on cells. We further made an effort to characterise the bioactive compounds causing these effects, using a combination of liquid chromatography methods followed by bioassaying and protein identification using proteomics. The outcomes of this study might prove valuable for better understanding venom-induced cell- and tissue-damaging pathologies and could be used in the process of developing and improving snakebite treatments.

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“…They also occur in spider venoms such as that of the orb-weaver spider ( Araneus ventricosus ) [ 20 ], as well as stingray venom [ 20 ], and tick saliva [ 19 ]. Cystatins make up as much as 9.8% of venom from the Gaboon viper Bitis gabonica gabonica , but the function of snake and spider venom cystatins is unknown [ 21 ]. It has been suggested that they may protect other venom components from prey proteases [ 21 ] or contribute to oral health like mammalian salivary cystatins [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cystatins make up as much as 9.8% of venom from the Gaboon viper Bitis gabonica gabonica , but the function of snake and spider venom cystatins is unknown [ 21 ]. It has been suggested that they may protect other venom components from prey proteases [ 21 ] or contribute to oral health like mammalian salivary cystatins [ 19 ]. However, H. rufovarius venom cystatin 1 was found to be the major proteinaceous component of a fraction that paralysed and killed flies (f93).…”

Section: Discussionmentioning

confidence: 99%

Crouching Tiger, Hidden Protein: Searching for Insecticidal Toxins in Venom of the Red Tiger Assassin Bug (Havinthus rufovarius)

Wait

Walker

King

2020

Toxins

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Assassin bugs are venomous insects that prey on other arthropods. Their venom has lethal, paralytic, and liquifying effects when injected into prey, but the toxins responsible for these effects are unknown. To identify bioactive assassin bug toxins, venom was harvested from the red tiger assassin bug (Havinthus rufovarius), an Australian species whose venom has not previously been characterised. The venom was fractionated using reversed-phase high-performance liquid chromatography, and four fractions were found to cause paralysis and death when injected into sheep blowflies (Lucilia cuprina). The amino acid sequences of the major proteins in two of these fractions were elucidated by comparing liquid chromatography/tandem mass spectrometry data with a translated venom-gland transcriptome. The most abundant components were identified as a solitary 12.8 kDa CUB (complement C1r/C1s, Uegf, Bmp1) domain protein and a 9.5 kDa cystatin. CUB domains are present in multidomain proteins with diverse functions, including insect proteases. Although solitary CUB domain proteins have been reported to exist in other heteropteran venoms, such as that of the bee killer assassin bug Pristhesancus plagipennis, their function is unknown, and they have not previously been reported as lethal or paralysis-inducing. Cystatins occur in the venoms of spiders and snakes, but again with an unknown function. Reduction and alkylation experiments revealed that the H. rufovarius venom cystatin featured five cysteine residues, one of which featured a free sulfhydryl group. These data suggest that solitary CUB domain proteins and/or cystatins may contribute to the insecticidal activity of assassin bug venom.

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Snake Venom Protease Inhibitors: Enhanced Identification, Expanding Biological Function, and Promising Future

Cited by 7 publications

References 102 publications

Exploring Toxin Genes of Myanmar Russell’s Viper, Daboia siamensis, through De Novo Venom Gland Transcriptomics

Exploring Toxin Genes of Myanmar Russell’s Viper, Daboia siamensis, through De Novo Venom Gland Transcriptomics

Development of a high-throughput in vitro screening method for the assessment of cell-damaging activities of snake venoms

Crouching Tiger, Hidden Protein: Searching for Insecticidal Toxins in Venom of the Red Tiger Assassin Bug (Havinthus rufovarius)

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