Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Arch Toxicol. 2024 Nov;98(11):3569-3584. doi: 10.1007/s00204-024-03849-5. Epub 2024 Aug 24.
Snakebite envenomation is a serious health concern in tropical regions, resulting in high mortality. The World Health Organization (WHO) has declared it a neglected tropical disease and is working on strategies to reduce mortality. Russell's viper (Daboia russelii) is one of the most abundant venomous snakes found across Southeast Asia. Proteomic analysis of Russell's viper venom has demonstrated variation, with phospholipase A2 (PLA2) being the most abundant toxin across geographic boundaries. PLA2, a major constituent of the low-molecular-weight fraction of snake venom, hydrolyses phospholipids at the sn-2 position, releasing arachidonic acid and lysophospholipids. They are reported to cause various pharmacological effects, including hemolysis, anticoagulation, neurotoxicity, myotoxicity, and oedema. Though administration of antivenoms (ASV) is the primary treatment for envenomation, it has many drawbacks. Besides causing hypersensitivity reactions and life-threatening anaphylaxis, treatment with ASV is further complicated due to its inability to neutralize low-molecular-weight toxins. Thus, there is a greater need to produce next-generation antivenoms that can target specific toxins in the venom. In this review, we explored the classification of Russell's viper and the variation in its proteomic profile across Southeast Asia to date. In addition, we have also summarized the mechanism of action of PLA2 and discussed various isoforms of PLA2 found across different regions with their respective pharmacological effects. Finally, the drawbacks of commercially available antivenoms and the molecules investigated for inhibiting the low-molecular-weight toxin, PLA2 are discussed.
蛇伤是热带地区严重的健康问题，导致死亡率很高。世界卫生组织（WHO）已将其宣布为被忽视的热带病，并正在制定策略以降低死亡率。圆斑蝰（Daboia russelii）是东南亚最丰富的毒蛇之一。圆斑蝰蛇毒的蛋白质组学分析表明存在变异，其中磷脂酶 A2（PLA2）是跨越地理边界最丰富的毒素。PLA2 是蛇毒低分子量部分的主要成分，在 sn-2 位置水解磷脂，释放花生四烯酸和溶血磷脂。据报道，它们会引起各种药理作用，包括溶血、抗凝、神经毒性、肌毒性和水肿。虽然抗蛇毒血清（ASV）的给药是蛇伤的主要治疗方法，但它存在许多缺点。除了引起过敏反应和威胁生命的过敏反应外，由于其不能中和低分子量毒素，ASV 的治疗变得更加复杂。因此，需要生产能够针对毒液中特定毒素的下一代抗蛇毒血清。在这篇综述中，我们探讨了圆斑蝰的分类以及迄今为止其蛋白质组在东南亚的变化。此外，我们还总结了 PLA2 的作用机制，并讨论了在不同地区发现的各种 PLA2 同工型及其各自的药理作用。最后，讨论了市售抗蛇毒血清的缺点以及用于抑制低分子量毒素 PLA2 的分子。
