Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, Australia.
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Autónoma de México, Av. Universidad 2001, Cuernavaca 62210, Mexico.
Toxins (Basel). 2022 Jul 26;14(8):511. doi: 10.3390/toxins14080511.
Within Neotropical pit-vipers, the Mexican/Central-American clade consisting of , , , and is a wide-ranging, morphologically and ecologically diverse group of snakes. Despite their prevalence, little is known of the functional aspects of their venoms. This study aimed to fill the knowledge gap regarding coagulotoxic effects and to examine the potential of different therapeutic approaches. As a general trait, the venoms were shown to be anticoagulant but were underpinned by diverse biochemical actions. Pseudo-procoagulant activity (i.e., thrombin-like), characterized by the direct cleavage of fibrinogen to form weak fibrin clots, was evident for , , and In contrast, other venoms cleaved fibrinogen in a destructive (non-clotting) manner, with and being the most potent. In addition to actions on fibrinogen, clotting enzymes were also inhibited. FXa was only weakly inhibited by most species, but and were extremely strong in their inhibitory action. Other clotting enzymes were more widely inhibited by diverse species spanning the full taxonomical range, but in each case, there were species that had these traits notably amplified relatively to the others. and were the most potent amongst those that inhibited the formation of the prothrombinase complex and were also amongst the most potent inhibitors of Factor XIa. While most species displayed only low levels of thrombin inhibition, potently inhibited this clotting factor. The regional polyvalent antivenom produced by Instituto Picado Clodomiro was tested and was shown to be effective against the diverse anticoagulant pathophysiological effects. In contrast to the anticoagulant activities of the other species, was uniquely procoagulant through the activation of Factor VII and Factor XII. This viperid species is the first snake outside of the elapid snake clade to be shown to activate FVII and the first snake venom of any kind to activate FXII. Interestingly, while small-molecule metalloprotease inhibitors prinomastat and marimastat demonstrated the ability to prevent the procoagulant toxicity of , neither ICP antivenom nor inhibitor DMPS showed this effect. The extreme variation among the snakes here studied underscores how venom is a dynamic trait and how this can shape clinical outcomes and influence evolving treatment strategies.
在新热带坑蝰蛇中，由 、 、 和 组成的中美洲/墨西哥分支是一个广泛分布的、形态和生态多样化的蛇类群体。尽管它们很普遍，但人们对它们毒液的功能方面知之甚少。本研究旨在填补这方面的知识空白，并研究不同治疗方法的潜力。一般来说，这些毒液是抗凝的，但具有不同的生化作用。假促凝血活性（即类似于凝血酶），表现为直接裂解纤维蛋白原形成弱纤维蛋白凝块，在 、 和 中是明显的。相比之下，其他毒液以破坏性（不凝固）的方式裂解纤维蛋白原，其中 和 最有效。除了对纤维蛋白原的作用外，凝血酶还被抑制。大多数物种对 FXa 的抑制作用较弱，但 和 的抑制作用非常强。其他凝血酶也被广泛抑制，涉及跨越整个分类范围的不同物种，但在每种情况下，都有一些物种的这些特性相对其他物种明显放大。 和 在抑制凝血酶原酶复合物形成方面是最强的，也是最强的 FXIa 抑制剂之一。虽然大多数物种只显示出低水平的凝血酶抑制作用，但 却能强烈抑制这种凝血因子。由 Clodomiro Picado 研究所生产的区域性多价抗蛇毒血清进行了测试，结果表明它对各种抗凝病理生理作用有效。与其他物种的抗凝活性相反， 通过激活因子 VII 和因子 XII 具有独特的促凝作用。这种坑蝰蛇是除眼镜蛇科蛇类以外的第一种被证明能激活 FVII 的蛇类，也是第一种能激活 FXII 的任何种类的蛇毒。有趣的是，虽然小分子金属蛋白酶抑制剂普洛美司他和马利司他显示出能够预防 的促凝毒性，但 ICP 抗蛇毒血清或抑制剂 DMPS 都没有显示出这种效果。本研究中研究的蛇类之间的巨大差异突出了毒液是一种动态特征，以及它如何影响临床结果和影响不断发展的治疗策略。
