The paraspecific neutralisation of snake venom induced coagulopathy by antivenoms

被引：82

作者：

Ainsworth, Stuart ^{[1
]}

Slagboom, Julien ^{[1
,2
]}

Alomran, Nessrin ^{[1
]}

Pla, Davinia ^{[3
]}

Alhamdi, Yasir ^{[4
]}

King, Sarah I. ^{[1
]}

Bolton, Fiona M. S. ^{[1
]}

Gutierrez, Jose Maria ^{[5
]}

Vonk, Freek J. ^{[6
]}

Toh, Cheng-Hock ^{[4
,7
]}

Calvete, Juan J. ^{[3
]}

Kool, Jeroen ^{[2
]}

Harrison, Robert A. ^{[1
,8
]}

Casewell, Nicholas R. ^{[1
,8
]}

机构：

[1] Univ Liverpool Liverpool Sch Trop Med, Alistair Reid Venom Res Unit, Dept Parasitol, Pembroke Pl, Liverpool L3 5QA, Merseyside, England

[2] Vrije Univ Amsterdam, Div BioAnalyt Chem, Dept Chem & Pharmaceut Sci, Fac Sci, NL-1081 LA Amsterdam, Netherlands

[3] CSIC, Lab Venom Estruct & Func, Inst Biomed Valencia, Valencia 46010, Spain

[4] Univ Liverpool, Inst Infect & Global Hlth, Liverpool L69 7BE, Merseyside, England

[5] Univ Costa Rica, Inst Clodomiro Picado, Fac Microbiol, San Jose 115012060, Costa Rica

[6] Nat Biodivers Ctr, NL-2333 CR Leiden, Netherlands

[7] Royal Liverpool Univ Hosp, Roald Dahl Haemostasis & Thrombosis Ctr, Liverpool L7 8XP, Merseyside, England

[8] Univ Liverpool Liverpool Sch Trop Med, Res Ctr Drugs & Diagnost, Pembroke Pl, Liverpool L3 5QA, Merseyside, England

来源：

COMMUNICATIONS BIOLOGY | 2018年 / 1卷

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

BOTHROPS-ASPER; CARPET VIPER; ECHIS-CARINATUS; IN-VIVO; METALLOPROTEINASE; INHIBITORS; STRATEGIES; BOOMSLANG; PHYLOGENY; THROMBIN;

D O I：

10.1038/s42003-018-0039-1

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Snake envenoming causes several potentially lethal pathologies. The specific pathology is dictated by the toxin composition of venom, which varies by species, geography and ontogeny. This variation severely restricts the paraspecific efficacy of antivenoms used to treat snakebite victims. With a view to devising pathology-specific snakebite treatments, we assessed the procoagulant activity of 57 snake venoms and investigated the efficacy of various antivenoms. We find that procoagulant venoms act differentially on key steps of the coagulation cascade, and that certain monospecific antivenoms work in a previously unrecognised paraspecific manner to neutralise this activity, despite conventional assumptions of congener-restricted efficacy. Moreover, we demonstrate that the metal chelator EDTA is also capable of neutralising venom-induced lethality in vivo. This study illustrates the exciting potential of developing new, broad-spectrum, toxin-targeting antivenoms capable of treating key snakebite pathologies, and advocates a thorough re-examination of enzyme inhibiting compounds as alternative therapies for treating snakebite victims.

引用

页数：14

共 62 条

[1] Chelation in metal intoxication-Principles and paradigms [J].