PDF(Pubmed)
Abstract：
Nipah virus infection, one of the top priority diseases recognized by the World Health Organization, underscores the urgent need to develop effective countermeasures against potential epidemics and pandemics. Here, we identify a fully human single-domain antibody that targets a highly conserved cryptic epitope situated at the dimeric interface of the Nipah virus G protein (receptor binding protein, RBP), as elucidated through structures by high-resolution cryo-electron microscopy (cryo-EM). This unique binding mode disrupts the tetramerization of the G protein, consequently obstructing the activation of the F protein and inhibiting viral membrane fusion. Furthermore, our investigations reveal that this compact antibody displays enhanced permeability across the blood-brain barrier (BBB) and demonstrates superior efficacy in eliminating pseudovirus within the brain in a murine model of Nipah virus infection, particularly compared to the well-characterized antibody m102.4 in an IgG1 format. Consequently, this single-domain antibody holds promise as a therapeutic candidate to prevent Nipah virus infections and has potential implications for vaccine development.
摘要：
尼帕病毒感染,世界卫生组织承认的最优先疾病之一，强调迫切需要针对潜在的流行病和大流行病制定有效的对策。这里,我们确定了一种完全人单结构域抗体，该抗体靶向位于尼帕病毒G蛋白（受体结合蛋白，RBP),通过高分辨率低温电子显微镜（cryo-EM）的结构阐明。这种独特的结合模式破坏了G蛋白的四聚化，因此阻碍了F蛋白的激活并抑制了病毒膜融合。此外，我们的研究表明，这种紧凑型抗体在血脑屏障（BBB）中显示出增强的通透性，并在尼帕病毒感染的鼠模型中在消除脑内假病毒方面表现出卓越的功效，特别是与IgG1形式的充分表征的抗体m102.4相比。因此,这种单结构域抗体有望作为预防尼帕病毒感染的治疗候选药物,并对疫苗开发具有潜在意义.
