A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2
A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2
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DOI：
10.1038/s41586-020-2381-y
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发表时间：
2020-05-26
期刊：
影响因子：
64.8
通讯作者：
Yan, Jinghua
中科院分区：
文献类型：
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作者：
Shi, Rui;Shan, Chao;Yan, Jinghua
由严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）（4）引起的2019年冠状病毒病（COVID-19）（1-3）爆发已在全球蔓延。需要采取对策来治疗和预防病毒的进一步传播。在这里，我们报告了从COVID-19康复患者中分离出两种特异性人单克隆抗体（称为CA 1和CB 6）。CA 1和CB 6在体外表现出有效的SARS-CoV-2特异性中和活性。此外，CB 6在预防和治疗环境中抑制了恒河猴中SARS-CoV-2的感染。我们还进行了结构研究，发现CB 6识别与SARS-CoV-2受体结合域中的血管紧张素转换酶2（ACE 2）结合位点重叠的表位，从而通过空间位阻和直接竞争界面残基来干扰病毒-受体相互作用。我们的研究结果表明，CB 6值得进一步研究，作为一个候选翻译到clinic.Two单克隆抗体分离自COVID-19患者显示干扰SARS-CoV-2受体结合，和一个显示在体外和恒河猴模型对这种病毒的有效作用。
An outbreak of coronavirus disease 2019 (COVID-19)(1-3), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(4), has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.Two monoclonal antibodies isolated from a patient with COVID-19 are shown to interfere with SARS-CoV-2-receptor binding, and one displays potent action against this virus in vitro and in a rhesus macaque model.