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Broad neutralization of SARS-CoV-2 variants by an inhalable bispecific single-domain antibody
Cheng Li; Wuqiang Zhan; Zhenlin Yang; Chao Tu; Yuanfei Zhu; Wenping Song; Keke Huang; Xiaodan Gu; Yu Kong; Xiang Zhang; Meng Zhang; Yi Zhang; Youhua Xie; Qiang Deng; Zhenguo Chen; Lu Lu; Shibo Jiang; Lei Sun; Yanling Wu; Tianlei Ying.
Affiliation
  • Cheng Li; Fudan University
  • Wuqiang Zhan; Fudan University
  • Zhenlin Yang; Fudan University
  • Chao Tu; Biomissile
  • Yuanfei Zhu; Fudan University
  • Wenping Song; Fudan University
  • Keke Huang; Fudan University
  • Xiaodan Gu; Fudan University
  • Yu Kong; Fudan University
  • Xiang Zhang; Fudan University
  • Meng Zhang; Fudan University
  • Yi Zhang; Biomissile
  • Youhua Xie; Fudan University
  • Qiang Deng; Fudan University
  • Zhenguo Chen; Fudan University
  • Lu Lu; Fudan University
  • Shibo Jiang; Fudan University
  • Lei Sun; Fudan University
  • Yanling Wu; Fudan University
  • Tianlei Ying; Fudan University
Preprint in English | bioRxiv | ID: ppbiorxiv-474535
ABSTRACT
The effectiveness of SARS-CoV-2 vaccines and therapeutic antibodies has been limited by the continuous emergence of viral variants, and by the restricted diffusion of antibodies from circulation into the sites of respiratory virus infection. Here, we report the identification of two highly conserved regions on Omicron variant RBD recognized by broadly neutralizing antibodies. Based on this finding, we generated a bispecific single-domain antibody that was able to simultaneously and synergistically bind these two regions on a single Omicron variant RBD as revealed by Cryo-EM structures. This inhalable antibody exhibited exquisite neutralization breadth and therapeutic efficacy in mouse models of SARS-CoV-2 infections. The structures also deciphered an uncommon cryptic epitope within the spike trimeric interface that may have implications for the design of broadly protective SARS-CoV-2 vaccines and therapeutics.
License
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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
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