The use of venom in predation exerts a corresponding selection pressure for the evolution of venom resistance. One of the mechanisms related to venom resistance in animals (predators or prey of snakes) is the presence of molecules in the blood that can bind venom toxins, and inhibit their pharmacological effects. One such toxin type are venom phospholipase A₂s (PLA₂s), which have diverse effects including anticoagulant, myotoxic, and neurotoxic activities. BoaγPLI isolated from the blood of Boa constrictor has been previously shown to inhibit venom PLA₂s that induced myotoxic and edematogenic activities. Recently, in addition to its previously described and very potent neurotoxic effect, the venoms of American coral snakes (Micrurus species) have been shown to have anticoagulant activity via PLA₂ toxins. As coral snakes eat other snakes as a major part of their diet, neonate Boas could be susceptible to predation by this sympatric species. Thus, this work aimed to ascertain if BoaγPLI provided a protective effect against the anticoagulant toxicity of venom from the model species Micrurus laticollaris in addition to its ability shown previously against other toxin types. Using a STA R Max coagulation analyser robot to measure the effect upon clotting time, and TEG5000 thromboelastographers to measure the effect upon clot strength, we evaluated the ability of BoaγPLI to inhibit M. laticollaris venom. Our results indicate that BoaγPLI is efficient at inhibiting the M. laticollaris anticoagulant effect, reducing the time of coagulation (restoring them closer to non-venom control values) and increasing the clot strength (restoring them closer to non-venom control values). These findings demonstrate that endogenous PLA₂ inhibitors in the blood of non-venomous snakes are multi-functional and provide broad resistance against a myriad of venom PLA₂-driven toxic effects including coagulotoxicity, myotoxicity, and neurotoxicity. This novel form of resistance could be evidence of selective pressures caused by predation from venomous snakes and stresses the need for field-based research aimed to expand our understanding of the evolutionary dynamics of such chemical arms race.

在捕食中使用毒液对毒液抗性的进化施加了相应的选择压力。与动物（捕食者或蛇的猎物）毒液抗性相关的机制之一是血液中存在可以结合毒液毒素并抑制其药理作用的分子。一种这样的毒素类型是毒液磷脂酶 A ₂ s (PLA ₂ s)，其具有多种作用，包括抗凝、肌毒性和神经毒性活性。从蟒蛇的血液中分离的 BoaγPLI先前已被证明可以抑制毒液 PLA ₂ s，后者会引起肌毒性和致水肿活性。最近，除了先前描述的非常有效的神经毒性作用外，美国珊瑚蛇的毒液（Micrurus物种）已被证明通过 PLA ₂毒素具有抗凝活性。由于珊瑚蛇以其他蛇类为食作为其饮食的主要组成部分，因此新生的蟒蛇可能容易受到这种同域物种的捕食。因此，这项工作旨在确定 BoaγPLI除了先前显示的针对其他毒素类型的能力之外，是否还提供了对来自模型物种Micrurus laticollaris的毒液的抗凝毒性的保护作用。我们使用 STA R Max 凝血分析仪机器人测量对凝血时间的影响，并使用 TEG5000 血栓弹力图仪测量对凝块强度的影响，我们评估了 BoaγPLI 抑制M. laticollaris的能力毒液。我们的结果表明 BoaγPLI 可有效抑制M. laticollaris抗凝作用，减少凝固时间（将它们恢复到更接近非毒液控制值）和增加凝块强度（将它们恢复到更接近非毒液控制值）。这些发现表明，无毒蛇血液中的内源性 PLA ₂抑制剂是多功能的，对无数毒液 PLA ₂具有广泛的抵抗力驱动的毒性作用包括凝血毒性、肌肉毒性和神经毒性。这种新的抗性形式可能是毒蛇捕食造成的选择性压力的证据，并强调了实地研究的必要性，旨在扩大我们对此类化学军备竞赛进化动力学的理解。