Venom Evolution Lab, School of Biological Science, University of Queensland, St. Lucia, QLD 4072, Australia.
Department of Biochemistry & Microbiology, North South University, Dhaka 1229, Bangladesh.
Toxins (Basel). 2022 Dec 1;14(12):836. doi: 10.3390/toxins14120836.
The African viperid snake genera , and are closely related, similar in size, but occupy extremely divergent ecological niches (arboreal in tropical rainforests, fossorial in deserts, and swamp-dwelling, respectively). Their venoms have not previously been subjected to comparative analyses for their action upon the coagulation of blood, most notably with significant data deficiencies from and In contrast, the closely related genus is well-documented as capable of producing potent procoagulant effects. In light of this, we set out to compare the coagulotoxic actions of , , , , , , , , and and explore potential pharmacological interventions to reestablish normal blood coagulation. All venoms displayed extremely potent procoagulant effects, over twice as fast as the most potent reported to date. Although is used in the immunising mixture of two different regionally available antivenoms (Inoserp-MENA with , , and Saudi Arabian polyvalent with ), none of the other species in this study are included in the immunising mixture of any antivenom. Notably, all the species were only neutralised by the Inoserp-MENA antivenom. venom was not neutralised well by the Saudi Arabian antivenom, with the low levels of recognition for any of the venoms suggesting a strong regional variation in the venom of this species, as the venom tested was of African (Tunisian) origin versus Saudi locality used in that antivenom's production. The other antivenoms (Micropharm EchiTAbG, ICP EchiTAb-Plus-ICP, Inosan Inoserp Pan-Africa, Premium Serums PANAF Sub-Sahara Africa, South African Vaccine Producers , South African Vaccine Producers Polyvalent) all displayed trivial-to-no ability to neutralise the procoagulant toxicity of any of the , or venoms. Comparative testing of the enzyme inhibitors DMPS, marimastat, and prinomastat, revealed a very potent neutralising capacity of marimastat, with prinomastat showing lower but still significant potency at the same molar concentration, while a 5× molar concentration of DMPS had no apparent effect on procoagulant venom effects normalized by the other inhibitors. These results and methods contribute to the body of knowledge of potential clinical effects and data necessary for evidence-based advancement of clinical management strategies.
非洲蝰蛇属和属密切相关，大小相似，但占据极其不同的生态位（热带雨林中的树栖动物、沙漠中的穴居动物和沼泽地中的动物）。它们的毒液以前没有进行过比较分析，以了解它们对血液凝固的作用，尤其是和属的数据严重不足。相比之下，密切相关的属被充分证明能够产生强烈的促凝作用。鉴于此，我们着手比较、、、、、、、和的凝血毒性作用，并探索潜在的药理学干预措施，以恢复正常的血液凝固。所有毒液都显示出极强的促凝作用，比迄今为止报道的最强毒液快两倍以上。虽然在两种不同的地区性抗蛇毒血清（Inoserp-MENA 与、和沙特阿拉伯多价）的免疫混合物中使用，但本研究中的其他物种都不包含在任何抗蛇毒血清的免疫混合物中。值得注意的是，只有 Inoserp-MENA 抗蛇毒血清能中和所有属的毒液。来自沙特阿拉伯的抗蛇毒血清不能很好地中和毒液，而且任何属毒液的识别水平都很低，这表明该物种的毒液在该地区存在强烈的变异，因为测试的毒液来自非洲（突尼斯），而沙特阿拉伯的毒液则来自于该抗蛇毒血清的生产地。其他抗蛇毒血清（Micropharm EchiTAbG、ICPEchiTAb-Plus-ICP、Inosan Inoserp Pan-Africa、Premium Serums PANAF Sub-Sahara Africa、南非疫苗生产商、南非疫苗生产商多价）均显示出对任何属或属毒液的促凝毒性几乎没有中和能力。对酶抑制剂 DMPS、marimastat 和 prinomastat 的比较测试表明，marimastat 具有很强的中和能力，而 prinomastat 在相同摩尔浓度下也具有较低但仍有显著的效力，而 5 倍摩尔浓度的 DMPS 对用其他抑制剂归一化的促凝毒液效应没有明显影响。这些结果和方法为潜在的临床效果和基于证据的临床管理策略提供了必要的知识体系。
