A steric block to SARS-CoV-2 In response to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the immune system makes antibodies, many of which target the spike protein, a key player in host cell entry. Antibodies that potently neutralize the virus hold promise as therapeutics and could inform vaccine design. Lv et al. report a humanized monoclonal antibody that protected against SARS-CoV-2 in a mouse model. The cryo–electron microscopy structure, together with biochemical, cellular, and virological studies, showed that the antibody acts by binding to the receptor-binding domain of the spike and blocking its attachment to the host receptor. Science, this issue p. 1505 An antibody protects against SARS-CoV-2 in a humanized mouse model by blocking the interaction of the virus with its receptor. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo–electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.

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一种有效的治疗性抗体中和 SARS-CoV-2 和 SARS-CoV 的结构基础

SARS-CoV-2 的空间阻滞 为了应对严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的感染，免疫系统会产生抗体，其中许多抗体针对刺突蛋白，刺突蛋白是宿主细胞进入的关键因素。有效中和病毒的抗体有望作为治疗剂，并可以为疫苗设计提供信息。吕等人。报告了一种在小鼠模型中针对 SARS-CoV-2 提供保护的人源化单克隆抗体。冷冻电子显微镜结构连同生化、细胞和病毒学研究表明，抗体通过与刺突的受体结合域结合并阻断其与宿主受体的连接来发挥作用。科学，这个问题 p。1505 一种抗体通过阻断病毒与其受体的相互作用，在人源化小鼠模型中抵御 SARS-CoV-2。由严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 引起的 2019 年冠状病毒病 (COVID-19) 大流行导致了前所未有的公共卫生危机。没有批准的疫苗或疗法来治疗 COVID-19。在这里，我们报告了一种人源化单克隆抗体 H014，它通过与尖峰 (S) 受体结合域 (RBD) 结合，以纳摩尔浓度有效中和 SARS-CoV-2 和 SARS-CoV 假病毒以及真正的 SARS-CoV-2。在人类血管紧张素转换酶 2 小鼠模型中，H014 给药降低了受感染肺部的 SARS-CoV-2 滴度，并预防了肺部病变。与 H014 Fab 片段复合的 SARS-CoV-2 S 三聚体的冷冻电子显微镜表征揭示了一个以前未表征的构象表位，只有当 RBD 处于开放构象时才能访问。生化、细胞、病毒学和结构研究表明，H014 可防止 SARS-CoV-2 附着在其宿主细胞受体上。针对 SARS-CoV 和 SARS-CoV-2 的可用中和抗体的表位分析发现了广泛的交叉保护表位。我们的结果强调了基于抗体的治疗干预在 COVID-19 治疗中的关键作用。