Redureau Damien, Amorim Fernanda Gobbi, Crasset Thomas, Berger Imre, Schaffitzel Christiane, Menzies Stefanie Kate, Casewell Nicholas R, Quinton Loïc
Laboratory of Mass Spectrometry, MolSys Research Unit, University of Liège, B4000 Liège, Belgium.
School of Biochemistry, University of Bristol, 1 Tankard's Close, Bristol BS8 1TD, UK.
Toxins (Basel). 2025 May 13;17(5):243. doi: 10.3390/toxins17050243.
Snakebite envenoming constitutes a significant global health issue, particularly in Africa, where venomous species such as vipers and mambas pose substantial risks to human health. This study employs a standardized venomics workflow to comprehensively characterize and comparatively quantify the venom composition of nine medically relevant snake species chosen from among the deadliest in Africa. Utilizing shotgun venom proteomics and venom gland transcriptomics, we report detailed profiles of venom complexity, highlighting the relative abundance of dominant toxin families such as three-finger toxins and Kunitz-type proteins in , and metalloproteinases and phospholipases A in . We delineate here the relative abundance and structural diversity of venom components. Key to our proteomic approach is the implementation of Multi-Enzymatic Limited Digestion (MELD), which improved protein sequence coverage and enabled the identification of rare toxin families such as hyaluronidases and renin-like proteases, by multiplying the overlap of generated peptides and enhancing the characterization of both toxin and non-toxin components within the venoms. The culmination of these efforts resulted in the construction of a detailed toxin database, providing insights into the biological roles and potential therapeutic targets of venom proteins and peptides. The findings here compellingly validate the MELD technique, reinforcing its reproducibility as a valuable characterization approach applied to venomics. This research significantly advances our understanding of venom complexity in African snake species, including representatives of both Viperidae and Elapidae families. By elucidating venom composition and toxin profiles, our study paves the way for the development of targeted therapies aimed at mitigating the morbidity and mortality associated with snakebite envenoming globally.
蛇咬伤中毒是一个重大的全球健康问题，在非洲尤为突出，那里的毒蛇如蝰蛇和曼巴蛇对人类健康构成了重大风险。本研究采用标准化的毒液组学工作流程，全面表征并比较定量从非洲最致命的蛇类中挑选出的9种具有医学相关性的蛇类的毒液成分。利用鸟枪法毒液蛋白质组学和毒腺转录组学，我们报告了毒液复杂性的详细概况，突出了主要毒素家族的相对丰度，如眼镜蛇三指毒素和库尼兹型蛋白，以及蝰蛇金属蛋白酶和磷脂酶A。我们在此描述了毒液成分的相对丰度和结构多样性。我们蛋白质组学方法的关键是实施多酶有限消化（MELD），通过增加生成肽段的重叠并增强毒液中毒素和非毒素成分的表征，提高了蛋白质序列覆盖率，并能够鉴定罕见的毒素家族，如透明质酸酶和肾素样蛋白酶。这些努力的成果是构建了一个详细的毒素数据库，为毒液蛋白质和肽的生物学作用及潜在治疗靶点提供了见解。此处的研究结果有力地验证了MELD技术，强化了其作为应用于毒液组学的一种有价值表征方法的可重复性。这项研究显著推进了我们对非洲蛇类毒液复杂性的理解，包括蝰蛇科和眼镜蛇科的代表物种。通过阐明毒液成分和毒素概况，我们的研究为开发旨在减轻全球蛇咬伤中毒相关发病率和死亡率的靶向疗法铺平了道路。
