Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain.
Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain.
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DOI：
10.1016/j.celrep.2023.113653
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发表时间：
2024-01
期刊：
影响因子：
8.8
通讯作者：
Yanqun Wang;Zhaoyong Zhang;Minnan Yang;Xinyi Xiong;Qihong Yan;Lei Cao;Peilan Wei;Yuting Zhang-Yutin
中科院分区：
文献类型：
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作者：
Yanqun Wang;Zhaoyong Zhang;Minnan Yang;Xinyi Xiong;Qihong Yan;Lei Cao;Peilan Wei;Yuting Zhang-Yutin
Omicron作为一种新出现的具有增强疫苗耐受性的变异体，已经急剧破坏了大多数治疗性抗体。严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）属于Sarbecovirus亚属，其成员具有高度的序列相似性。在此，我们报告了一个Sarbecovirus抗体，5817，它具有广谱中和能力，对SARS-CoV-2变异的关注（VOCs）和SARS-CoV，以及相关的蝙蝠和穿山甲病毒。5817几乎不能与按结构分类分组的六类受体结合域靶向抗体竞争。未检测到对SARS-CoV-2 Omicron和亚变体的效力的明显损害。与Omicron刺突复合的中和抗体5817的冷冻电子显微镜（cryo-EM）结构揭示了一个高度保守的表位，仅存在于受体结合结构域（RBD）开放状态。5817的预防性和治疗性给药有效地保护小鼠免受SARS-CoV-2 Beta、Delta、Omicron和SARS-CoV感染。这项研究揭示了一个高度保守的隐蔽表位靶向广泛的Sarbecovirus中和抗体，这将是有益的，以满足潜在的威胁，紧急SARS-CoV-2 VOCs。
Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs.