Ainsworth Stuart, Slagboom Julien, Alomran Nessrin, Pla Davinia, Alhamdi Yasir, King Sarah I, Bolton Fiona M S, Gutiérrez José María, Vonk Freek J, Toh Cheng-Hock, Calvete Juan J, Kool Jeroen, Harrison Robert A, Casewell Nicholas R
Alistair Reid Venom Research Unit, Parasitology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, Vrije Universiteit Amsterdam, Amsterdam, 1081 LA, The Netherlands.
Commun Biol. 2018 Apr 19;1:34. doi: 10.1038/s42003-018-0039-1. eCollection 2018.
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.
蛇咬伤会引发多种潜在致命的病理状况。具体的病理状况取决于毒液的毒素成分,而毒液成分会因蛇的种类、地理分布和个体发育情况而有所不同。这种差异严重限制了用于治疗蛇咬伤受害者的抗蛇毒血清的种间特异性疗效。为了设计针对特定病理状况的蛇咬伤治疗方法,我们评估了57种蛇毒的促凝血活性,并研究了各种抗蛇毒血清的疗效。我们发现,具有促凝血作用的蛇毒对凝血级联反应的关键步骤有不同的作用,而且某些单价抗蛇毒血清以一种此前未被认识的种间特异性方式发挥作用来中和这种活性,尽管传统观念认为其疗效受同属限制。此外,我们证明金属螯合剂乙二胺四乙酸(EDTA)在体内也能够中和毒液诱导的致死性。这项研究说明了开发能够治疗关键蛇咬伤病理状况的新型、广谱、靶向毒素的抗蛇毒血清的令人兴奋的潜力,并主张对酶抑制化合物作为治疗蛇咬伤受害者的替代疗法进行全面重新审视。