Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences/University of Chinese Academy of Sciences, Shanghai, China.
CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (CAS), Shanghai, China.
PLoS Pathog. 2023 Jan 27;19(1):e1011085. doi: 10.1371/journal.ppat.1011085. eCollection 2023 Jan.
Neutralizing antibodies (nAbs) are important assets to fight COVID-19, but most existing nAbs lose the activities against Omicron subvariants. Here, we report a human monoclonal antibody (Ab08) isolated from a convalescent patient infected with the prototype strain (Wuhan-Hu-1). Ab08 binds to the receptor-binding domain (RBD) with pico-molar affinity (230 pM), effectively neutralizes SARS-CoV-2 and variants of concern (VOCs) including Alpha, Beta, Gamma, Mu, Omicron BA.1 and BA.2, and to a lesser extent for Delta and Omicron BA.4/BA.5 which bear the L452R mutation. Of medical importance, Ab08 shows therapeutic efficacy in SARS-CoV-2-infected hACE2 mice. X-ray crystallography of the Ab08-RBD complex reveals an antibody footprint largely in the β-strand core and away from the ACE2-binding motif. Negative staining electron-microscopy suggests a neutralizing mechanism through which Ab08 destructs the Spike trimer. Together, our work identifies a nAb with therapeutic potential for COVID-19.
中和抗体（nAbs）是对抗 COVID-19 的重要资产，但大多数现有的 nAbs 失去了对奥密克戎亚变种的活性。在这里，我们报告了一种从感染原型株（武汉-Hu-1）的康复患者中分离出来的人源单克隆抗体（Ab08）。Ab08 以皮摩尔亲和力（230pM）结合受体结合域（RBD），有效中和 SARS-CoV-2 及其关注变种（VOCs），包括 Alpha、Beta、Gamma、Mu、Omicron BA.1 和 BA.2，对携带 L452R 突变的 Delta 和 Omicron BA.4/BA.5 的中和活性则较低。具有医学重要性的是，Ab08 在感染 SARS-CoV-2 的 hACE2 小鼠中显示出治疗效果。Ab08-RBD 复合物的 X 射线晶体学揭示了抗体足迹主要在β-折叠核心，远离 ACE2 结合基序。负染色电子显微镜提示了一种中和机制，通过该机制 Ab08 破坏了 Spike 三聚体。总之，我们的工作鉴定了一种具有治疗 COVID-19 潜力的 nAb。
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