CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Nature. 2020 Aug;584(7819):120-124. doi: 10.1038/s41586-020-2381-y. Epub 2020 May 26.
An outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 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.
新型冠状病毒病（COVID-19）是由严重急性呼吸系统综合征冠状病毒 2 型（SARS-CoV-2）引起的一种传染病，已在全球范围内传播。需要采取措施来治疗和预防病毒的进一步传播。在这里，我们报告了从一名 COVID-19 康复患者中分离出的两种特异性人源单克隆抗体（称为 CA1 和 CB6）。CA1 和 CB6 在体外均表现出针对 SARS-CoV-2 的强大中和活性。此外，CB6 还可在恒河猴中预防和治疗 SARS-CoV-2 感染。我们还进行了结构研究，揭示了 CB6 识别的表位与 SARS-CoV-2 受体结合域中的血管紧张素转换酶 2（ACE2）结合位点重叠，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，CB6 值得进一步研究，作为一种向临床转化的候选药物。
