Venom Evolution Lab, School of Biological Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran 1983969411, Iran.
Int J Mol Sci. 2021 Jun 27;22(13):6896. doi: 10.3390/ijms22136896.
Venoms are a rich source of potential lead compounds for drug discovery, and descriptive studies of venom form the first phase of the biodiscovery process. In this study, we investigated the pharmacological potential of crude and snake venoms in haematological disorders and cancer treatment. We assessed their antithrombotic potential using fibrinogen thromboelastography, fibrinogen gels with and without protease inhibitors, and colourimetric fibrinolysis assays. These assays indicated that the anticoagulant properties of the venoms are likely induced by the hydrolysis of phospholipids and by selective fibrinogenolysis. Furthermore, while most fibrinogenolysis occurred by the direct activity of snake venom metalloproteases and serine proteases, modest evidence indicated that fibrinogenolytic activity may also be mediated by selective venom phospholipases and an inhibitory venom-derived serine protease. We also found that the venoms significantly reduced the viability of human melanoma (MM96L) cells by more than 80%, while it had almost no effect on the healthy neonatal foreskin fibroblasts (NFF) as determined by viability assays. The bioactive properties of these venoms suggest that they contain a number of toxins suitable for downstream pharmacological development as candidates for antithrombotic or anticancer agents.
毒液是药物发现的潜在先导化合物的丰富来源，对毒液的描述性研究构成了生物发现过程的第一阶段。在这项研究中，我们研究了粗制蛇毒液在血液疾病和癌症治疗中的药理潜力。我们使用纤维蛋白原血栓弹性描记术、有和没有蛋白酶抑制剂的纤维蛋白原凝胶以及比色纤维蛋白溶解测定法来评估它们的抗血栓形成潜力。这些测定法表明，毒液的抗凝特性可能是由磷脂的水解和选择性纤维蛋白原水解引起的。此外，虽然大多数纤维蛋白原水解是通过蛇毒金属蛋白酶和丝氨酸蛋白酶的直接活性发生的，但有一些证据表明，纤维蛋白原水解活性也可能通过选择性的毒液磷脂酶和抑制性毒液衍生的丝氨酸蛋白酶介导。我们还发现，毒液显著降低了人黑色素瘤（MM96L）细胞的活力，超过 80%，而通过活力测定法，它对健康的新生儿包皮成纤维细胞（NFF）几乎没有影响。这些毒液的生物活性特性表明，它们含有许多适合下游药理学开发的毒素，可作为抗血栓形成或抗癌药物的候选物。
