Cross reactivity and lethality neutralization of venoms of Indonesian Trimeresurus complex species by Thai Green Pit Viper Antivenom

Tan, Choo Hock; Liew, Jia Lee; Tan, Nget Hong; Ismail, Ahmad Khaldun; Maharani, Tri; Khomvilai, Sumana; Sitprija, Visith

doi:10.1016/j.toxicon.2017.10.014

Cited by 40 publications

(33 citation statements)

References 30 publications

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“…These laboratory findings are consistent with the haemorrhagic clinical manifestations of envenomation by Trimeresurus species (Chan et al, 1993;Chotenimitkhun and Rojnuckarin, 2008;Cockram et al, 1990;Greene et al, 2017;Hutton et al, 1990;Rojnuckarin et al, 2007;Rojnuckarin et al, 1999;Tan et al, 2017a;Visudhiphan et al, 1989;Witharana et al, 2019;Wongtongkam et al, 2005). In particular, the venoms have been shown clinically to produce rapid and pronounced decrease in fibrinogen levels leading to a net anticoagulant state (Collet et al, 2000;Longstaff and Kolev, 2015;Ryan et al, 1999), which is consistent with the results presented here.…”

Section: Discussionsupporting

confidence: 91%

“…Further, this prior study did not attempt to determine the effect fibrinogen cleavage had upon clotting or the ability of antivenom to neutralise these pathological effects. In addition, prior studies also only measured antivenom binding through the use ELISA or Western Blot, which would reveal only simple antivenom binding to venom proteins, with no kinetic information, and, crucially prior studies did not ascertain whether the antivenom was effective in neutralising the venom's pathological functions (Jones et al, 2019;Tan et al, 2017a). In contrast, in this study we not only quantified the effects upon fibrinogen but also investigated the ability of the Thai Red Cross Green Pit Viper Antivenin to neutralise the coagulotoxic effects of the 13 species of Trimeresurus investigated here.…”

Section: Discussionmentioning

confidence: 99%

“…flavomaculatus, T. insularis, T. macrops, T. purpureomaculatus, and T. stejnegeri (Clark and Davidson, 1997;Jones et al, 2019;Mitrakul, 1973;Rojnuckarin et al, 1999;Tai et al, 2004;Tan et al, 2017a;Tan, 2010;Tan et al, 1994;Visudhiphan et al, 1989;Witharana et al, 2019;Wongtongkam et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…It has been established in the literature that venom composition between closely related species, or within different populations of a single species, may vary considerably due to differential pressures regarding prey availability and prey escape potential. This variation has direct implications for the relative clinical usefulness of antivenoms against species not included in the immunising mixture, or varying populations of the species used (Debono et al, 2017a;Dobson et al, 2018;Fry et al, 2003a;Lister et al, 2017;Rogalski et al, 2017;Sousa et al, 2018;Sunagar et al, 2014;Tan et al, 2017a;Yang et al, 2016;Zdenek et al, 2019). Many current antivenomic strategies are mostly limited to the immunoreactivity of the antivenom towards the venom components, these do not ascertain whether the antivenom is effective in neutralising venom pathological functions (Jones et al, 2019;Williams et al, 2011;Xu et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…albolabris envenomation and venom composition has been the centre of much research focus (Chotenimitkhun and Rojnuckarin, 2008;Greene et al, 2017;Hutton et al, 1990;Lin et al, 2009;Muanpasitporn and Rojnuckarin, 2007;Peng et al, 1992;Pradniwat and Rojnuckarin, 2015;Rojnuckarin et al, 1999;Tan et al, 2017a;Tan et al, 2012) and is the main Trimeresurus species targeted by available antivenoms, such as the monovalent Green Pit Viper Antivenin produced by the Thai Red Cross. However, in many of the regions where Trimeresurus species exist, a specific antivenom is lacking (Tan et al, 2017a). Moreover, the venom composition and function of most other species within the genus have been comparably neglected, with a few exceptions such as T.…”

Section: Introductionmentioning

confidence: 99%

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A blood bond: evolutionary, pathophysiological and biodiscovery implications of coagulotoxic snake venoms

Debono¹

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Snakebite is a massive global burden and is a neglected area of tropical diseases. Snake venom neurotoxins have been the subject of intense research efforts, albeit significantly less is known about coagulotoxins. Venoms can deleteriously affect any physiological system reachable by the bloodstream, including being able to directly interfere with the coagulation cascade. Such coagulopathic toxins may be either anticoagulant or procoagulant and snake venoms are unique in their use of procoagulant toxins for predatory purposes. Our limited knowledge into the mechanisms of action of snake venom hinders our understanding of the clinical pathologies and also restricts our use of these powerful natural products as lead compounds in drug design and development. Two snake families which exhibit coagulant properties and lead to a range of clinical pathologies are vipers, Viperidae, and non-front-fanged snakes, Colubridae. The primary focus of this thesis was to investigate and compare the coagulotoxicity effects and mechanisms of various species of known venomous snakes that effect coagulation. Species chosen for this investigation have had limited previous research conducted, thus a knowledge gap in the literature remains. These coagulant properties were investigated through a multi-disciplinary approach, highlighting key results from both families.Data chapters 2 and 3 explore venom from the boomslang (Dispholidus typus) and the twig snakes (Thelotornis species) -iconic African snakes belonging to the family Colubridae. Both species produce strikingly similar lethal procoagulant pathologies. Despite these similarities, antivenom is only produced for treating bites by D. typus, and the mechanisms of action of both venoms have been understudied. We found that T. mossambicanus produced a significantly stronger coagulation response compared to D. typus, governed by strong prothrombin activation through PIII-SVMPs.Despite similarities in symptoms and clinical manifestations, venom composition differs widely between the two species, recovered from a combined approach of venomics and transcriptomics. The neutralising capability of the available boomslang antivenom was also investigated on both species, with it being 11.3 times more effective upon D. typus venom than T. mossambicanus. Envenomation by Crotalinae such as Asian pit vipers can induce multiple clinical complications resulting from coagulopathic and neuropathic effects. Data chapters 4 -8 investigate the Asian Pit Viper clade. While intense research has been undertaken for some species, such as Calloselasma rhodostoma, functional coagulopathic effects have been neglected. As these species' venoms affect the blood coagulation cascade and are known to produce haemorrhagic shock in envenomed patients, we investigated their effects upon coagulation using venoms of 33 species from the Asian pit viper clade including Azemiops, Calloselasma, Deinagkistrodon, Gloydius, Hypnale, Protobothrops, Trimeresurus and Tropidolaemus. Fibrinogen was the main coagulation target among th...

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