两种抗体通过诱导 RBD 的构象变化,对 SARS-CoV-2 变体显示出广泛的协同中和作用。

IF 13.6 1区 生物学 Q1 CELL BIOLOGY
Hui Sun, Tingting Deng, Yali Zhang, Yanling Lin, Yanan Jiang, Yichao Jiang, Yang Huang, Shuo Song, Lingyan Cui, Tingting Li, Hualong Xiong, Miaolin Lan, Liqin Liu, Yu Li, Qianjiao Fang, Kunyu Yu, Wenling Jiang, Lizhi Zhou, Yuqiong Que, Tianying Zhang, Quan Yuan, Tong Cheng, Zheng Zhang, Hai Yu, Jun Zhang, Wenxin Luo, Shaowei Li, Qingbing Zheng, Ying Gu, Ningshao Xia
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引用次数: 0

摘要

严重急性呼吸系统综合症冠状病毒(SARS-CoV-2)病毒的不断进化使其能够逐渐躲避因自然感染或接种疫苗而产生的中和抗体(nAbs)。这些变化的快速性促使人们需要开发优良的广谱 nAbs(bnAbs)和/或合理设计能抵御变异病毒株的鸡尾酒抗体。在这里,我们报告了两种血管紧张素转换酶 2 竞争性 nAbs-8H12 和 3E2--它们具有协同中和作用,但被一些 Omicron 亚变体所规避。冷冻电镜显示,这两种 nAbs 通过受体结合结构域中 472-489 环的重新排列实现了严格配对,避免了立体冲突,从而协同中和了病毒。基于这两种 nAbs 的双特异性抗体极大地扩展了中和广度,并恢复了对包括目前占主导地位的 XBB.1.5 在内的最新变体的中和作用。总之,这些发现拓展了我们对中和 SARS-CoV-2 变体的潜在策略的理解,有助于我们设计广效抗体疗法和疫苗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Two antibodies show broad, synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD.

Continual evolution of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus has allowed for its gradual evasion of neutralizing antibodies (nAbs) produced in response to natural infection or vaccination. The rapid nature of these changes has incited a need for the development of superior broad nAbs (bnAbs) and/or the rational design of an antibody cocktail that can protect against the mutated virus strain. Here, we report two angiotensin-converting enzyme 2 competing nAbs-8H12 and 3E2-with synergistic neutralization but evaded by some Omicron subvariants. Cryo-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric clashing. Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant XBB.1.5. Together, these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

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来源期刊
Protein & Cell
Protein & Cell CELL BIOLOGY-
CiteScore
24.00
自引率
0.90%
发文量
1029
审稿时长
6-12 weeks
期刊介绍: Protein & Cell is a monthly, peer-reviewed, open-access journal focusing on multidisciplinary aspects of biology and biomedicine, with a primary emphasis on protein and cell research. It publishes original research articles, reviews, and commentaries across various fields including biochemistry, biophysics, cell biology, genetics, immunology, microbiology, molecular biology, neuroscience, oncology, protein science, structural biology, and translational medicine. The journal also features content on research policies, funding trends in China, and serves as a platform for academic exchange among life science researchers.
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