明尼苏达大学医学院李放团队在研究中取得进展。他们提出了马尔堡病毒糖蛋白的结构及其与NPC1受体的复合物。这一研究成果于2026年3月11日发表在国际顶尖学术期刊《自然》上。

本研究表明MBV糖蛋白（GP）比EBOV糖蛋白更有效地介导病毒进入。利用低温电镜（cryo-EM）测定了MBV GP在三种状态下的结构：(1)未结合状态；(2)与其内体受体NPC1结合；(3)与中和纳米体络合。聚糖帽保护受体结合位点不受NPC1的影响，但只能部分地保护纳米体不受NPC1的影响，从而实现有限的免疫逃避。在糖帽裂解后，NPC1以与EBOV GP不同的方向与MBV GP结合，提供额外的锚点并增强受体亲和力。NPC1的参与也诱导了MBV GP的构象变化，可能促进了膜离子的形成。

此外，MBV GP易受中和纳米体的影响，中和纳米体在受体结合位点模仿NPC1。总之，他们的发现揭示了MBV GP是一种高效的进入介质，并提出了可能有助于其提高进入效率的结构机制。

据介绍，马尔堡病毒主题（MBVs）是严重出血热，死亡率高于埃博拉病毒（EBOV）。

附：英文原文

Title: Structures of Marburgvirus glycoprotein and its complex with NPC1 receptor

Author: Ye, Gang, Bu, Fan, Turner-Hubbard, Hailey, Herbst, Morgan, Du, Lanying, Yang, Ge, Liu, Bin, Li, Fang

Issue&Volume: 2026-03-11

Abstract: Marburgviruses (MBVs) cause severe haemorrhagic fever with higher fatality rates than Ebola virus (EBOV)1,2,3,4. Here we show that the MBV glycoprotein (GP) mediates viral entry more efficiently than EBOV GP. Using cryo-EM, we determined structures of MBV GP in three states: (1) unbound; (2) bound to its endosomal receptor NPC1; and (3) complexed with a neutralizing nanobody. The glycan cap shields the receptor-binding site from NPC1 but only partially from the nanobody, enabling limited immune evasion. After glycan cap cleavage, NPC1 binds to MBV GP in a distinct orientation compared with EBOV GP, providing an additional anchor and enhancing receptor affinity. NPC1 engagement also induces substantial conformational changes in MBV GP, probably facilitating membrane fusion. Furthermore, MBV GP is susceptible to the neutralizing nanobody, which mimics NPC1 at the receptor-binding site. Together, our findings reveal MBV GP as a highly efficient entry mediator and suggest structural mechanisms that may contribute to its enhanced entry efficiency.

DOI: 10.1038/s41586-026-10240-0

Source: https://www.nature.com/articles/s41586-026-10240-0