论文标题：The paraspecific neutralisation of snake venom induced coagulopathy by antivenoms

期刊：Communications Biology

作者：Stuart Ainsworth, Julien Slagboom, Nessrin Alomran, Davinia Pla, Yasir Alhamdi, Sarah I. King, Fiona M. S. Bolton, José María Gutiérrez, Freek J. Vonk, Cheng-Hock Toh, Juan J. Calvete, Jeroen Kool, Robert A. Harrison & Nicholas R. Casewell

发表时间： 2018/04/19

数字识别码： 10.1038/s42003-018-0039-1

原文链接：https://www.nature.com/articles/s42003-018-0039-1?utm_source=Other_website&utm_medium=Website_links&utm_content=RenLi-Nature-Communications_Biology-Biology-China&utm_campaign=NEWCOMMS_USG_rlp8212_snake_sciencenet_article_June_3rd

全世界每年有上百万人在热带地区被蛇咬伤和超过十万人因此死亡。如果有足够的对蛇种专一的抗蛇毒血清，这些死亡完全可以避免。抗蛇毒血清的昂贵和短缺的原因在于它的制造程序仍遵循上世纪的传统。

由于蛇种的地理分布和每种毒素的不同成分，抗蛇毒血清的制造是在不同的地区针对不同的蛇种进行。各地的研究蛇毒的机构会大量繁殖当地的蛇种，在上万次的少量收集每一种蛇毒之后，把蛇毒分别注入专门为此饲养的动物，比如马或者羊，然后进行重复的抽血。由于制作的时间较长和人力成本的因素，每个完整的抗蛇毒血清疗程的费用高达几万美金， 这也导致了最容易被蛇咬伤的生活在热带农村的群体成为了最没能力负担疗程的群体。

图一：在哥斯达黎加圣马兰岛拍摄到的一条毒蛇。

Photo by Alfonso Castro

为了降低抗蛇毒血清疗程的费用和普及其应用，英国利物浦热带医学学院的阿拉斯泰尔-里德蛇毒研究单位里由 Nick Casewell博士带领的研究团队挑战了传统的制造抗蛇毒血清的策略，并于《通讯-生物学》期刊上发文（The paraspecific neutralisation of snake venom induced coagulopathy by antivenoms）。他们不再把蛇毒以地理区域划分，而是在病理层面上把蛇毒划分为四类：促凝血的，导致血流不止的，给神经系统带来损伤的，和导致细胞组织坏死的。他们设想，把抗蛇毒血清按以上四类集中生产，然后向各地输送，会大幅度地降低其生产成本。

Casewell博士的团队先集中研究促凝血的蛇毒。他们评估了57种蛇毒的促凝血活性，并比较了各种抗蛇毒血清的疗效。他们发现多数促凝血的蛇毒的分子机制都针对凝血级联通路里的几个核心的蛋白。他们还发现有些抗蛇毒血清对多种不同的蛇毒有交叉反应，这和之前的研究数据相符。这些数据支持了他们用病理把蛇毒分类的设想。沿着这个思路，他们制造出针对一种蛇毒但是能够中和多种蛇毒的抗体。最后，他们证明金属螯合剂乙二胺四乙酸（EDTA）也能够在小老鼠体内中和蛇毒。这些策略有制造抗蛇毒血清的经济替代品的潜力。

Nick Casewell博士说：“我们希望能够发展一个可以应用于全球的、用规模经济大幅度地降低成本的模式，还有找出能够替代现在极昂贵的抗蛇毒血清的酶， 从而让低收入的蛇咬伤者得到帮助。”

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.

阅读论文全文请访问：https://www.nature.com/articles/s42003-018-0039-1?utm_source=Other_website&utm_medium=Website_links&utm_content=RenLi-Nature-Communications_Biology-Biology-China&utm_campaign=NEWCOMMS_USG_rlp8212_snake_sciencenet_article_June_3rd

期刊介绍：Communications Biology (https://www.nature.com/commsbio/) is an open access journal from Nature Research publishing high-quality research, reviews and commentary in all areas of the biological sciences. Research papers published by the journal represent significant advances bringing new biological insight to a specialized area of research.（来源：科学网）