非洲毒蛇属Atheris,Cerastes,和Proatheris密切相关,大小相似,但占据了极其不同的生态位(热带雨林中的树栖动物,在沙漠中,和沼泽居住,分别)。它们的毒液以前没有对它们对血液凝固的作用进行比较分析,最值得注意的是,Atheris和Proatheris的数据存在重大缺陷。相比之下,紧密相关的Echis属被证明能够产生有效的促凝血作用。鉴于此,我们着手比较Ceratophora的凝血毒性作用,A.chlorechis,A.德赛希,A.Nitschei,A.squamigera,C.cerastes,C.cerastes gasperettii,C.vipera,并探索潜在的药物干预措施以重建正常的凝血功能。所有毒液都显示出极其有效的促凝血作用,比迄今为止报道的最有效的Echis快两倍多。尽管Cerastes用于两种不同的区域性抗蛇毒血清的免疫混合物(Inoserp-MENA与C.cerastes,C.cerastes gasperettii,C.vipera和沙特阿拉伯与C.cerastes多价),本研究中的其他物种均不包括在任何抗蛇毒血清的免疫混合物中。值得注意的是,所有Cerastes物种仅被Inoserp-MENA抗蛇毒血清中和。C.cerastes毒液没有被沙特阿拉伯抗蛇毒血清很好地中和,对任何一种Cerastes毒液的认可度都很低,这表明该物种的毒液存在很大的区域差异,因为测试的C.cerastes毒液来自非洲(突尼斯),而在该抗蛇毒血清生产中使用的沙特阿拉伯地区。其他抗蛇毒血清(MicropharmEchiTAbG,ICPEchiTab-Plus-ICP,InosanInoserp泛非洲,优质血清PANAF撒哈拉以南非洲,南非疫苗生产商Echis,南非疫苗生产商多价)都显示出微不足道的能力,以中和任何Atheris的促凝血毒性,Cerastes,或Proatheris毒液。酶抑制剂DMPS的比较测试,marimastat,和prinomastat,显示出marimastat非常强大的中和能力,在相同的摩尔浓度下,prinomastat显示出更低但仍然显著的效力,而DMPS的5×摩尔浓度对其他抑制剂归一化的促凝血毒液效果没有明显影响。这些结果和方法有助于了解潜在的临床效果和基于证据的临床管理策略的发展所需的数据。
The African viperid snake genera Atheris, Cerastes, and Proatheris 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 Atheris and Proatheris. In contrast, the closely related genus Echis is well-documented as capable of producing potent procoagulant effects. In light of this, we set out to compare the coagulotoxic actions of Atheris ceratophora, A. chlorechis, A. desaixi, A. nitschei, A. squamigera, C. cerastes, C. cerastes gasperettii, C. vipera, and Proatheris superciliaris 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 Echis reported to date. Although Cerastes is used in the immunising mixture of two different regionally available antivenoms (Inoserp-MENA with C. cerastes, C. cerastes gasperettii, C. vipera and Saudi Arabian polyvalent with C. cerastes), none of the other species in this study are included in the immunising mixture of any antivenom. Notably, all the Cerastes species were only neutralised by the Inoserp-MENA antivenom. C. cerastes venom was not neutralised well by the Saudi Arabian antivenom, with the low levels of recognition for any of the Cerastes venoms suggesting a strong regional variation in the venom of this species, as the C. cerastes 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 Echis, South African Vaccine Producers Polyvalent) all displayed trivial-to-no ability to neutralise the procoagulant toxicity of any of the Atheris, Cerastes, or Proatheris 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.