Since their first identification 50 years ago, marburgviruses have emerged several times, with 83%-90% lethality in the largest outbreaks. Although no vaccines or therapeutics are available for human use, the human antibody MR191 provides complete protection in non-human primates when delivered several days after inoculation of a lethal marburgvirus dose. The detailed neutralization mechanism of MR191 remains outstanding. Here we present a 3.2 Å crystal structure of MR191 complexed with a trimeric marburgvirus surface glycoprotein (GP). MR191 neutralizes by occupying the conserved receptor-binding site and competing with the host receptor Niemann-Pick C1. The structure illuminates previously disordered regions of GP including the stalk, fusion loop, CX6CC switch, and an N-terminal region of GP2 that wraps about the outside of GP1 to anchor a marburgvirus-specific "wing" antibody epitope. Virus escape mutations mapped far outside the MR191 receptor-binding site footprint suggest a role for these other regions in the GP quaternary structure.

中文翻译：

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马尔堡病毒中和性人类单克隆抗体MR191靶向保守位点以阻断病毒受体结合。

自从50年前首次鉴定以来，马尔堡病毒已经出现了好几次，在最大的爆发中杀伤力达到83％-90％。尽管尚无可用于人类的疫苗或治疗剂，但在接种致命性马尔堡病毒剂量后数天交付时，人抗体MR191可在非人灵长类动物中提供完全保护。MR191的详细中和机制仍然很出色。在这里，我们介绍了与三聚体马尔堡病毒表面糖蛋白（GP）复合的MR191的3.2Å晶体结构。MR191通过占据保守的受体结合位点并与宿主受体Niemann-Pick C1竞争来中和。该结构照亮了GP先前无序的区域，包括茎，融合环，CX6CC开关，GP2的N末端区域包裹在GP1的外部，以锚定马尔堡病毒特异性“翼”抗体表位。映射到MR191受体结合位点足迹之外的病毒逃逸突变提示了GP四级结构中这些其他区域的作用。