We report the isolation and characterization of an alpaca-derived, single domain antibody fragment (nanobody) that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein (spike) and potently neutralizes the virus. A cryo-electron microscopy structure of the bound complex at 2.9 Å resolution reveals that the nanobody (Ty1) binds to an epitope on the RBD accessible in both the "up" and "down" conformations and that Ty1 sterically hinders RBD-ACE2 binding. Mechanistic characterization confirms that Ty1 directly interferes with host cell receptor binding. This 12.8 kDa nanobody binds the SARS-CoV-2 spike with high specificity and affinity, and can be produced in high quantities recombinantly thereby offering potential as a potent and widely accessible SARS-CoV-2 antiviral agent.

中文翻译：

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羊驼纳米抗体通过阻断受体相互作用来中和SARS-CoV-2。

我们报告了羊驼来源的单域抗体片段（纳米抗体）的分离和表征，该片段特异性靶向SARS-CoV-2穗糖蛋白（穗）的受体结合域（RBD），并有效地中和病毒。结合的复合物在2.9Å分辨率下的冷冻电子显微镜结构表明，纳米抗体（Ty1）结合到RBD上的一个“上”和“下”构象均可访问的表位，并且Ty1在空间上阻碍了RBD-ACE2的结合。机理鉴定证实Ty1直接干扰宿主细胞受体结合。这种12.8 kDa的纳米抗体以高特异性和亲和力结合SARS-CoV-2尖峰，可以大量重组生产，从而有潜力作为有效且广泛使用的SARS-CoV-2抗病毒剂。