Snakebite is a neglected tropical disease with a massive global burden of injury and death. The best current treatments, antivenoms, are plagued by a number of logistical issues that limit supply and access in remote or poor regions. We explore the anticoagulant properties of venoms from the genus Micrurus (coral snakes), which have been largely unstudied, as well as the effectiveness of antivenom and a small-molecule phospholipase inhibitor-varespladib-at counteracting these effects. Our in vitro results suggest that these venoms likely interfere with the formation or function of the prothrombinase complex. We find that the anticoagulant potency varies widely across the genus and is especially pronounced in M. laticollaris. This variation does not appear to correspond to previously described patterns regarding the relative expression of the three-finger toxin and phospholipase A2 (PLA2) toxin families within the venoms of this genus. The coral snake antivenom Coralmyn, is largely unable to ameliorate these effects except for M. ibiboboca. Varespladib on the other hand completely abolished the anticoagulant activity of every venom. This is consistent with the growing body of results showing that varespladib may be an effective treatment for a wide range of toxicity caused by PLA2 toxins from many different snake species. Varespladib is a particularly attractive candidate to help alleviate the burden of snakebite because it is an approved drug that possesses several logistical advantages over antivenom including temperature stability and oral availability.

中文翻译：

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抗凝 Micrurus 毒液：目标和中和

蛇咬伤是一种被忽视的热带疾病，造成巨大的全球伤害和死亡负担。目前最好的治疗方法是抗蛇毒血清，但受到一系列物流问题的困扰，这些问题限制了偏远或贫困地区的供应和获取。我们探索了 Micrurus（珊瑚蛇）属毒液的抗凝特性，这在很大程度上尚未得到研究，以及抗蛇毒血清和小分子磷脂酶抑制剂 - 伐瑞拉迪 - 在抵消这些影响方面的有效性。我们的体外结果表明，这些毒液可能会干扰凝血酶原酶复合物的形成或功能。我们发现抗凝效力在整个属中差异很大，在 M. laticollaris 中尤其明显。这种变异似乎与先前描述的关于该属毒液中三指毒素和磷脂酶 A2 (PLA2) 毒素家族的相对表达的模式不符。除了 M. ibiboboca 之外，珊瑚蛇抗蛇毒血清 Coralmyn 在很大程度上无法改善这些影响。另一方面，Varespladib 完全消除了每种毒液的抗凝活性。这与越来越多的结果一致，表明伐瑞拉迪可能是一种有效治疗由来自许多不同蛇种的 PLA2 毒素引起的广泛毒性的方法。Varespladib 是一种特别有吸引力的候选药物，可帮助减轻蛇咬伤的负担，因为它是一种已获批准的药物，与抗蛇毒血清相比，具有多种物流优势，包括温度稳定性和口服可用性。