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A broadly neutralizing antibody inhibits SARS-CoV-2 variants through a novel mechanism of disrupting spike trimer integrity

Cell Research volume 33, pages 975–978 (2023)Cite this article

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Dear Editor,

Since the start of the COVID-19 pandemic, thousands of neutralizing antibodies (NAbs) targeting different epitopes of the spike protein have been identified and characterized.1,2,3 However, the emergence of the Omicron variant and its subvariants has raised global concern due to their resistance to most reported monoclonal antibodies and dramatically decreases the immune efficacy of current vaccines.4,5 A newly emerging subvariant XBB.1.16 that is rapidly disseminating on a global scale has been associated with a previously unreported symptom of red or pink eye.6 Compared to XBB.1.5, XBB.1.16 harbors two additional mutations, E180V and K478R, which are hypothesized to confer enhanced transmissibility and antigenic escape.7 The enhanced capacity of XBB.1.16 for transmission and immune evasion poses a greater threat to public health. Therefore, continuous efforts toward the rapid isolation and engineering of antibodies with cross-reactivity and potently neutralizing epitope specificities are essential to aid in the containment of COVID-19 in the face of viral genomic alterations.

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Fig. 1: 6i18 inhibits SARS-CoV-2 variants through a novel mechanism of disrupting S trimer integrity.

Data availability

The coordinates and maps associated with data reported in this manuscript have been deposited to the Electron Microscopy Data Bank (EMDB) and Protein Data Bank (PDB) under accession numbers EMD-36322 and PDB 8JIO, respectively.

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Acknowledgements

We thank the Center of Cryo-Electron Microscopy, Fudan University, for the support on cryo-EM data collection. This work was supported by the National Natural Science Foundation of China (32370995 and 31771008 to J.H. and 3197014 to Z.C.), the Shanghai Municipal Science and Technology Major Project (ZD2021CY001 to J.H.), the Ministry of Science and Technology of China (2021YFC2302500 to L.S.), the National Youth Talent Support Program (2022 to F.W.), the “Shuguang Program” of Shanghai Education Development Foundation and Shanghai Municipal Education Commission (22SG16 to F.W.), Guangzhou Laboratory (SRPG22-003 to L.S.), the National Science and Technology Major Projects of China (2017ZX10202102 to J.H. and 2018ZX10301403 to F.W.).

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Author notes

  1. These authors contributed equally: Yunping Ma, Qiyu Mao, Yingdan Wang, Zhaoyong Zhang.

Authors and Affiliations

  1. Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS) and Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Public Health Clinical Center, Shanghai Fifth People’s Hospital, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Yunping Ma, Qiyu Mao, Yingdan Wang, Jiali Chen, Aihua Hao, Palizhati Rehati, Yumei Wen, Lu Lu, Zhenguo Chen, Lei Sun & Jinghe Huang

  2. Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China

    Yunping Ma & Fan Wu

  3. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China

    Zhaoyong Zhang, Yanqun Wang & Jincun Zhao

  4. Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, Shanghai Tech University, Shanghai, China

    Jincun Zhao

Authors
  1. Yunping Ma
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Contributions

J.H., L.S., and F.W. conceived and designed the manuscript. J.H., F.W., Y.M., Y.D.W., J.C., P.R., and L.L. sorted B cells and cloned antibodies, constructed SARS-CoV-2 pseudovirus mutants, performed neutralization assay, ELISA, and BLI. L.S., Q.M., A.H., and Z.C. performed the structural studies. J.Z., Z.Z., and Y.Q.W. performed authentic virus experiments. Y.W. supervised the project. J.H., Y.M., Y.D.W., L.S., A.H., and Z.Z. analyzed the data. J.H., L.S., F.W., Y.D.W., and A.H. wrote the manuscript.

Corresponding authors

Correspondence to Jincun Zhao, Fan Wu, Lei Sun or Jinghe Huang.

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The authors declare no competing interests.

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Ma, Y., Mao, Q., Wang, Y. et al. A broadly neutralizing antibody inhibits SARS-CoV-2 variants through a novel mechanism of disrupting spike trimer integrity. Cell Res 33, 975–978 (2023). https://doi.org/10.1038/s41422-023-00880-6

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