Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. Our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. Structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable for the development of antibodies that target conserved epitopes among antigenically diverse targets, and it offers a promising framework for the creation of a monoclonal antibody–based universal antivenom to treat snakebite envenoming.

中文翻译：

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抗蛇毒长链α-神经毒素的广泛中和抗体的合成开发

蛇咬伤是全球主要的公共卫生问题，迫切需要改进的治疗方法。不同物种的蛇毒毒素中存在的抗原多样性对通用抗蛇毒血清的开发提出了相当大的挑战。在这里，我们使用合成的人类抗体库来寻找和开发一种抗体，该抗体可以中和许多医学相关蛇产生的长链三指 α-神经毒素。我们的抗体以高亲和力结合多种毒素变体，在体外阻断毒素与烟碱乙酰胆碱受体的结合，并保护小鼠免受致命毒液攻击。抗体-毒素复合物的结构分析揭示了模拟受体-毒素相互作用的结合模式。所提出的整体工作流程可推广用于开发针对抗原多样化目标中保守表位的抗体，并且它为创建基于单克隆抗体的通用抗蛇毒血清来治疗蛇咬伤提供了一个有前景的框架。