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Defining the pathogenic threat of envenoming by South African shield-nosed and coral snakes (genus Aspidelaps), and revealing the likely efficacy of available antivenom.
J Proteomics. 2019 04 30; 198:186-198.JP

Abstract

While envenoming by the southern African shield-nosed or coral snakes (genus Aspidelaps) has caused fatalities, bites are uncommon. Consequently, this venom is not used in the mixture of snake venoms used to immunise horses for the manufacture of regional SAIMR (South African Institute for Medical Research) polyvalent antivenom. Aspidelaps species are even excluded from the manufacturer's list of venomous snakes that can be treated by this highly effective product. This leaves clinicians, albeit rarely, in a therapeutic vacuum when treating envenoming by these snakes. This is a significantly understudied small group of nocturnal snakes and little is known about their venom compositions and toxicities. Using a murine preclinical model, this study determined that the paralysing toxicity of venoms from Aspidelaps scutatus intermedius, A. lubricus cowlesi and A. l. lubricus approached that of venoms from highly neurotoxic African cobras and mambas. This finding was consistent with the cross-genus dominance of venom three-finger toxins, including numerous isoforms which showed extensive interspecific variation. Our comprehensive analysis of venom proteomes showed that the three Aspidelaps species possess highly similar venom proteomic compositions. We also revealed that the SAIMR polyvalent antivenom cross-reacted extensively in vitro with venom proteins of the three Aspidelaps. Importantly, this cross-genus venom-IgG binding translated to preclinical (in a murine model) neutralisation of A. s. intermedius venom-induced lethality by the SAIMR polyvalent antivenom, at doses comparable with those that neutralise venom from the cape cobra (Naja nivea), which the antivenom is directed against. Our results suggest a wider than anticipated clinical utility of the SAIMR polyvalent antivenom, and here we seek to inform southern African clinicians that this readily available antivenom is likely to prove effective for victims of Aspidelaps envenoming. BIOLOGICAL

SIGNIFICANCE:

Coral and shield-nosed snakes (genus Aspidelaps) comprise two species and several subspecies of potentially medically important venomous snakes distributed in Namibia, Botswana, Zimbabwe, Mozambique and South Africa. Documented human fatalities, although rare, have occurred from both A. lubricus and A. scutatus. However, their venom proteomes and the pathological effects of envenomings by this understudied group of nocturnal snakes remain uncharacterised. Furthermore, no commercial antivenom is made using venom from species of the genus Aspidelaps. To fill this gap, we have conducted a transcriptomics-guided comparative proteomics analysis of the venoms of the intermediate shield-nose snake (A. s. intermedius), southern coral snake (A. l. lubricus), and Cowle's shield snake (A. l. cowlesi); investigated the mechanism of action underpinning lethality by A. s. intermedius in the murine model; and assessed the in vitro immunoreactivity of the SAIMR polyvalent antivenom towards the venom toxins of A. l. lubricus and A. l. cowlesi, and the in vivo capability of this antivenom at neutralising the lethal effect of A. s. intermedius venom. Our data revealed a high degree of conservation of the global composition of the three Aspidelaps venom proteomes, all characterised by the overwhelming predominance of neurotoxic 3FTxs, which induced classical signs of systemic neurotoxicity in mice. The SAIMR polyvalent antivenom extensively binds to Aspidelaps venom toxins and neutralised, with a potency of 0.235 mg venom/mL antivenom, the lethal effect of A. s. intermedius venom. Our data suggest that the SAIMR antivenom could be a useful therapeutic tool for treating human envenomings by Aspidelaps species.

Authors+Show Affiliations

Alistair Reid Venom Research Unit, Parasitology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.Alistair Reid Venom Research Unit, Parasitology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. Electronic address: nicholas.casewell@lstmed.ac.uk.Evolutionary and Translational Venomics Laboratory, CSIC, Jaime Roig 11, 46010, Valencia, Spain.Evolutionary and Translational Venomics Laboratory, CSIC, Jaime Roig 11, 46010, Valencia, Spain.Alistair Reid Venom Research Unit, Parasitology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. Electronic address: rhiannon.logan@lstmed.ac.uk.Alistair Reid Venom Research Unit, Parasitology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. Electronic address: fiona.bolton@lstmed.ac.uk.Bioinformatics Unit, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. Electronic address: simon.wagstaff@lstmed.ac.uk.Instituto Clodomiro Picado, Facultad de Microbiolgía, Universidad de Costa Rica, San José 11501-2060, Costa Rica. Electronic address: jose.gutierrez@ucr.ac.cr.Evolutionary and Translational Venomics Laboratory, CSIC, Jaime Roig 11, 46010, Valencia, Spain. Electronic address: jcalvete@ibv.csic.es.Alistair Reid Venom Research Unit, Parasitology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. Electronic address: robert.harrison@lstmed.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30290233

Citation

Whiteley, Gareth, et al. "Defining the Pathogenic Threat of Envenoming By South African Shield-nosed and Coral Snakes (genus Aspidelaps), and Revealing the Likely Efficacy of Available Antivenom." Journal of Proteomics, vol. 198, 2019, pp. 186-198.
Whiteley G, Casewell NR, Pla D, et al. Defining the pathogenic threat of envenoming by South African shield-nosed and coral snakes (genus Aspidelaps), and revealing the likely efficacy of available antivenom. J Proteomics. 2019;198:186-198.
Whiteley, G., Casewell, N. R., Pla, D., Quesada-Bernat, S., Logan, R. A. E., Bolton, F. M. S., Wagstaff, S. C., Gutiérrez, J. M., Calvete, J. J., & Harrison, R. A. (2019). Defining the pathogenic threat of envenoming by South African shield-nosed and coral snakes (genus Aspidelaps), and revealing the likely efficacy of available antivenom. Journal of Proteomics, 198, 186-198. https://doi.org/10.1016/j.jprot.2018.09.019
Whiteley G, et al. Defining the Pathogenic Threat of Envenoming By South African Shield-nosed and Coral Snakes (genus Aspidelaps), and Revealing the Likely Efficacy of Available Antivenom. J Proteomics. 2019 04 30;198:186-198. PubMed PMID: 30290233.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Defining the pathogenic threat of envenoming by South African shield-nosed and coral snakes (genus Aspidelaps), and revealing the likely efficacy of available antivenom. AU - Whiteley,Gareth, AU - Casewell,Nicholas R, AU - Pla,Davinia, AU - Quesada-Bernat,Sarai, AU - Logan,Rhiannon A E, AU - Bolton,Fiona M S, AU - Wagstaff,Simon C, AU - Gutiérrez,José M, AU - Calvete,Juan J, AU - Harrison,Robert A, Y1 - 2018/10/02/ PY - 2018/07/25/received PY - 2018/09/15/revised PY - 2018/09/30/accepted PY - 2018/10/6/pubmed PY - 2020/7/9/medline PY - 2018/10/6/entrez KW - Aspidelaps venoms toxicity KW - Genus Aspidelaps KW - Snake venom gland transcriptomics KW - Snake venom proteome KW - South african shield-nosed and coral snakes KW - Third-generation antivenomics KW - in vitro and in vivo preclinical assays SP - 186 EP - 198 JF - Journal of proteomics JO - J Proteomics VL - 198 N2 - While envenoming by the southern African shield-nosed or coral snakes (genus Aspidelaps) has caused fatalities, bites are uncommon. Consequently, this venom is not used in the mixture of snake venoms used to immunise horses for the manufacture of regional SAIMR (South African Institute for Medical Research) polyvalent antivenom. Aspidelaps species are even excluded from the manufacturer's list of venomous snakes that can be treated by this highly effective product. This leaves clinicians, albeit rarely, in a therapeutic vacuum when treating envenoming by these snakes. This is a significantly understudied small group of nocturnal snakes and little is known about their venom compositions and toxicities. Using a murine preclinical model, this study determined that the paralysing toxicity of venoms from Aspidelaps scutatus intermedius, A. lubricus cowlesi and A. l. lubricus approached that of venoms from highly neurotoxic African cobras and mambas. This finding was consistent with the cross-genus dominance of venom three-finger toxins, including numerous isoforms which showed extensive interspecific variation. Our comprehensive analysis of venom proteomes showed that the three Aspidelaps species possess highly similar venom proteomic compositions. We also revealed that the SAIMR polyvalent antivenom cross-reacted extensively in vitro with venom proteins of the three Aspidelaps. Importantly, this cross-genus venom-IgG binding translated to preclinical (in a murine model) neutralisation of A. s. intermedius venom-induced lethality by the SAIMR polyvalent antivenom, at doses comparable with those that neutralise venom from the cape cobra (Naja nivea), which the antivenom is directed against. Our results suggest a wider than anticipated clinical utility of the SAIMR polyvalent antivenom, and here we seek to inform southern African clinicians that this readily available antivenom is likely to prove effective for victims of Aspidelaps envenoming. BIOLOGICAL SIGNIFICANCE: Coral and shield-nosed snakes (genus Aspidelaps) comprise two species and several subspecies of potentially medically important venomous snakes distributed in Namibia, Botswana, Zimbabwe, Mozambique and South Africa. Documented human fatalities, although rare, have occurred from both A. lubricus and A. scutatus. However, their venom proteomes and the pathological effects of envenomings by this understudied group of nocturnal snakes remain uncharacterised. Furthermore, no commercial antivenom is made using venom from species of the genus Aspidelaps. To fill this gap, we have conducted a transcriptomics-guided comparative proteomics analysis of the venoms of the intermediate shield-nose snake (A. s. intermedius), southern coral snake (A. l. lubricus), and Cowle's shield snake (A. l. cowlesi); investigated the mechanism of action underpinning lethality by A. s. intermedius in the murine model; and assessed the in vitro immunoreactivity of the SAIMR polyvalent antivenom towards the venom toxins of A. l. lubricus and A. l. cowlesi, and the in vivo capability of this antivenom at neutralising the lethal effect of A. s. intermedius venom. Our data revealed a high degree of conservation of the global composition of the three Aspidelaps venom proteomes, all characterised by the overwhelming predominance of neurotoxic 3FTxs, which induced classical signs of systemic neurotoxicity in mice. The SAIMR polyvalent antivenom extensively binds to Aspidelaps venom toxins and neutralised, with a potency of 0.235 mg venom/mL antivenom, the lethal effect of A. s. intermedius venom. Our data suggest that the SAIMR antivenom could be a useful therapeutic tool for treating human envenomings by Aspidelaps species. SN - 1876-7737 UR - https://www.unboundmedicine.com/medline/citation/30290233/Defining_the_pathogenic_threat_of_envenoming_by_South_African_shield_nosed_and_coral_snakes__genus_Aspidelaps__and_revealing_the_likely_efficacy_of_available_antivenom_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1874-3919(18)30360-9 DB - PRIME DP - Unbound Medicine ER -