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Coagulotoxic effects by brown snake (Pseudonaja) and taipan (Oxyuranus) venoms, and the efficacy of a new antivenom.
Toxicol In Vitro 2019; 58:97-109TV

Abstract

Snakebite is a neglected tropical disease that disproportionately affects the poor. Antivenom is the only specific and effective treatment for snakebite, but its distribution is severely limited by several factors, including the prohibitive cost of some products. Papua New Guinea (PNG) is a snakebite hotspot but the high costs of Australian antivenoms (thousands of dollars per treatment) makes it unaffordable in PNG. A more economical taipan antivenom has recently been developed at the Instituto Clodomiro Picado (ICP) in Costa Rica for PNG and is currently undergoing clinical trials for the treatment of envenomations by coastal taipans (Oxyuranus scutellatus). In addition to potentially having the capacity to neutralise the effects of envenomations of non-PNG taipans, this antivenom may have the capacity to neutralise coagulotoxins in venom from closely related brown snakes (Pseudonaja spp.) also found in PNG. Consequently, we investigated the cross-reactivity of taipan antivenom across the venoms of all Oxyuranus and Pseudonaja species. In addition, to ascertain differences in venom biochemistry that influence variation in antivenom efficacy, we tested for relative cofactor dependence. We found that the new ICP taipan antivenom exhibited high selectivity for Oxyuranus venoms and only low to moderate cross-reactivity with any Pseudonaja venoms. Consistent with this genus level distinction in antivenom efficacy were fundamental differences in the venom biochemistry. Not only were the Pseudonaja venoms significantly more procoagulant, but they were also much less dependent upon the cofactors calcium and phospholipid. There was a strong correlation between antivenom efficacy, clotting time and cofactor dependence. This study sheds light on the structure-function relationships of the procoagulant toxins within these venoms and may have important clinical implications including for the design of next-generation antivenoms.

Authors+Show Affiliations

Venom Evolution Lab, School of Biological Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia.Venom Evolution Lab, School of Biological Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia; Reptile Kingdom Australia, Carrara, QLD, Australia.Department of Biosciences, College of Science, Swansea University, SA2 8PP, United Kingdom.Australian Venom Research Unit, Department of Pharmacology and Therapeutics, University of Melbourne, 3010, VIC, Australia.Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands.Venom Evolution Lab, School of Biological Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia.Venom Evolution Lab, School of Biological Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia.Venom Supplies Pty Ltd, Stonewell Rd, Tanunda, SA 5352, Australia.Venom Supplies Pty Ltd, Stonewell Rd, Tanunda, SA 5352, Australia.Adelaide Zoo, Adelaide, SA 5000, Australia.Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José 11501-2060, Costa Rica.Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José 11501-2060, Costa Rica.Australian Venom Research Unit, Department of Pharmacology and Therapeutics, University of Melbourne, 3010, VIC, Australia; Charles Campbell Toxinology Centre, School of Medicine and Health Sciences, University of Papua New Guinea, Boroko 121, National Capital District, Papua New Guinea.Venom Evolution Lab, School of Biological Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia. Electronic address: bgfry@uq.edu.au.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30910521

Citation

Zdenek, Christina N., et al. "Coagulotoxic Effects By Brown Snake (Pseudonaja) and Taipan (Oxyuranus) Venoms, and the Efficacy of a New Antivenom." Toxicology in Vitro : an International Journal Published in Association With BIBRA, vol. 58, 2019, pp. 97-109.
Zdenek CN, Hay C, Arbuckle K, et al. Coagulotoxic effects by brown snake (Pseudonaja) and taipan (Oxyuranus) venoms, and the efficacy of a new antivenom. Toxicol In Vitro. 2019;58:97-109.
Zdenek, C. N., Hay, C., Arbuckle, K., Jackson, T. N. W., Bos, M. H. A., Op den Brouw, B., ... Fry, B. G. (2019). Coagulotoxic effects by brown snake (Pseudonaja) and taipan (Oxyuranus) venoms, and the efficacy of a new antivenom. Toxicology in Vitro : an International Journal Published in Association With BIBRA, 58, pp. 97-109. doi:10.1016/j.tiv.2019.03.031.
Zdenek CN, et al. Coagulotoxic Effects By Brown Snake (Pseudonaja) and Taipan (Oxyuranus) Venoms, and the Efficacy of a New Antivenom. Toxicol In Vitro. 2019;58:97-109. PubMed PMID: 30910521.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Coagulotoxic effects by brown snake (Pseudonaja) and taipan (Oxyuranus) venoms, and the efficacy of a new antivenom. AU - Zdenek,Christina N, AU - Hay,Chris, AU - Arbuckle,Kevin, AU - Jackson,Timothy N W, AU - Bos,Mettine H A, AU - Op den Brouw,Bianca, AU - Debono,Jordan, AU - Allen,Luke, AU - Dunstan,Nathan, AU - Morley,Terry, AU - Herrera,María, AU - Gutiérrez,José M, AU - Williams,David J, AU - Fry,Bryan G, Y1 - 2019/03/22/ PY - 2018/08/09/received PY - 2019/03/12/revised PY - 2019/03/21/accepted PY - 2019/3/27/pubmed PY - 2019/3/27/medline PY - 2019/3/27/entrez KW - Antivenom KW - Coagulopathy KW - Coagulotoxic KW - Disseminated intravascular coagulation KW - ICP antivenom KW - Oxyuranus KW - Prothrombinase complex KW - Pseudonaja KW - Venom KW - Venom induced consumptive coagulopathy SP - 97 EP - 109 JF - Toxicology in vitro : an international journal published in association with BIBRA JO - Toxicol In Vitro VL - 58 N2 - Snakebite is a neglected tropical disease that disproportionately affects the poor. Antivenom is the only specific and effective treatment for snakebite, but its distribution is severely limited by several factors, including the prohibitive cost of some products. Papua New Guinea (PNG) is a snakebite hotspot but the high costs of Australian antivenoms (thousands of dollars per treatment) makes it unaffordable in PNG. A more economical taipan antivenom has recently been developed at the Instituto Clodomiro Picado (ICP) in Costa Rica for PNG and is currently undergoing clinical trials for the treatment of envenomations by coastal taipans (Oxyuranus scutellatus). In addition to potentially having the capacity to neutralise the effects of envenomations of non-PNG taipans, this antivenom may have the capacity to neutralise coagulotoxins in venom from closely related brown snakes (Pseudonaja spp.) also found in PNG. Consequently, we investigated the cross-reactivity of taipan antivenom across the venoms of all Oxyuranus and Pseudonaja species. In addition, to ascertain differences in venom biochemistry that influence variation in antivenom efficacy, we tested for relative cofactor dependence. We found that the new ICP taipan antivenom exhibited high selectivity for Oxyuranus venoms and only low to moderate cross-reactivity with any Pseudonaja venoms. Consistent with this genus level distinction in antivenom efficacy were fundamental differences in the venom biochemistry. Not only were the Pseudonaja venoms significantly more procoagulant, but they were also much less dependent upon the cofactors calcium and phospholipid. There was a strong correlation between antivenom efficacy, clotting time and cofactor dependence. This study sheds light on the structure-function relationships of the procoagulant toxins within these venoms and may have important clinical implications including for the design of next-generation antivenoms. SN - 1879-3177 UR - https://www.unboundmedicine.com/medline/citation/30910521/Coagulotoxic_effects_by_brown_snake_(Pseudonaja)_and_taipan_(Oxyuranus)_venoms,_and_the_efficacy_of_a_new_antivenom L2 - https://linkinghub.elsevier.com/retrieve/pii/S0887-2333(18)30439-9 DB - PRIME DP - Unbound Medicine ER -