An antibody defense against COVID-19 One of the responses of the immune system to invading viruses is the production of antibodies. Some of these are neutralizing, meaning that they prevent the virus from being infectious, and can thus be used to treat viral diseases. Wu et al. isolated four neutralizing antibodies from a convalescent coronavirus disease 2019 (COVID-19) patient. Two of the antibodies, B38 and H4, blocked the receptor binding domain (RBD) of the viral spike protein from binding to the cellular receptor, angiotensin-converting enzyme 2 (ACE2). The structure of the RBD bound to B38 shows that the B38-binding site overlaps with the binding site for ACE2. Although H4 also blocks RBD binding to ACE2, it binds at a different site, and thus the two antibodies can bind simultaneously. This pair of antibodies could potentially be used together in clinical applications. Science, this issue p. 1274 A pair of neutralizing antibodies against COVID-19 bind to different epitopes to compete with cellular receptor binding. Neutralizing antibodies could potentially be used as antivirals against the coronavirus disease 2019 (COVID-19) pandemic. Here, we report isolation of four human-origin monoclonal antibodies from a convalescent patient, all of which display neutralization abilities. The antibodies B38 and H4 block binding between the spike glycoprotein receptor binding domain (RBD) of the virus and the cellular receptor angiotensin-converting enzyme 2 (ACE2). A competition assay indicated different epitopes on the RBD for these two antibodies, making them a potentially promising virus-targeting monoclonal antibody pair for avoiding immune escape in future clinical applications. Moreover, a therapeutic study in a mouse model validated that these antibodies can reduce virus titers in infected lungs. The RBD-B38 complex structure revealed that most residues on the epitope overlap with the RBD-ACE2 binding interface, explaining the blocking effect and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide a structural basis for rational vaccine design.

中文翻译：

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一对非竞争性人类中和抗体可阻断 COVID-19 病毒与其受体 ACE2 的结合


针对 COVID-19 的抗体防御 免疫系统对入侵病毒的反应之一是产生抗体。其中一些具有中和作用，这意味着它们可以防止病毒具有传染性，因此可用于治疗病毒性疾病。吴等人。从 2019 年冠状病毒病 (COVID-19) 恢复期患者体内分离出四种中和抗体。其中两种抗体 B38 和 H4 可阻断病毒刺突蛋白的受体结合域 (RBD) 与细胞受体血管紧张素转换酶 2 (ACE2) 的结合。与 B38 结合的 RBD 结构表明 B38 结合位点与 ACE2 的结合位点重叠。虽然H4也阻断RBD与ACE2的结合，但它结合在不同的位点，因此两种抗体可以同时结合。这对抗体有可能在临床应用中一起使用。科学，本期第 14 页。 1274 一对针对 COVID-19 的中和抗体与不同的表位结合，与细胞受体结合竞争。中和抗体有可能用作对抗 2019 年冠状病毒病 (COVID-19) 大流行的抗病毒药物。在这里，我们报告从一名康复患者体内分离出四种人源单克隆抗体，所有这些抗体均表现出中和能力。抗体 B38 和 H4 阻断病毒的刺突糖蛋白受体结合域 (RBD) 与细胞受体血管紧张素转换酶 2 (ACE2) 之间的结合。竞争测定表明这两种抗体的 RBD 上有不同的表位，使它们成为潜在有前途的病毒靶向单克隆抗体对，可避免未来临床应用中的免疫逃逸。 此外，一项小鼠模型的治疗研究证实，这些抗体可以降低受感染肺部的病毒滴度。 RBD-B38复合物结构揭示表位上的大部分残基与RBD-ACE2结合界面重叠，解释了阻断效应和中和能力。我们的结果强调了基于抗体的疗法的前景，并为合理的疫苗设计提供了结构基础。