Three Ebolavirus genus viruses cause lethal disease and lack targeted therapeutics: Ebola virus, Sudan virus and Bundibugyo virus. Monoclonal antibody (mAb) cocktails against the surface glycoprotein (GP) present a potential therapeutic strategy. Here we report two crystal structures of the antibody BDBV223, alone and complexed with its GP2 stalk epitope, an interesting site for therapeutic/vaccine design due to its high sequence conservation among ebolaviruses. BDBV223, identified in a human survivor of Bundibugyo virus disease, neutralizes both Bundibugyo virus and Ebola virus, but not Sudan virus. Importantly, the structure suggests that BDBV223 binding interferes with both the trimeric bundle assembly of GP and the viral membrane by stabilizing a conformation in which the monomers are separated by GP lifting or bending. Targeted mutagenesis of BDBV223 to enhance SUDV GP recognition indicates that additional determinants of antibody binding likely lie outside the visualized interactions, and perhaps involve quaternary assembly or membrane-interacting regions.

三种埃博拉病毒属病毒引起致命的疾病，缺乏针对性的疗法：埃博拉病毒，苏丹病毒和邦迪布约病毒。针对表面糖蛋白（GP）的单克隆抗体（mAb）混合物提供了一种潜在的治疗策略。在这里，我们报告了抗体BDBV223的两个晶体结构，单独存在并与它的GP2茎表位复合，由于其在埃博拉病毒中具有较高的序列保守性，因此是治疗/疫苗设计的一个有趣位点。在Bundibugyo病毒疾病的人类幸存者中鉴定出的BDBV223可中和Bundibugyo病毒和Ebola病毒，但不会中和苏丹病毒。重要的是，该结构表明BDBV223结合通过稳定构象来干扰GP的三聚体束组装和病毒膜，在构象中，单体通过GP提升或弯曲而分离。