Neutralizing Antibodies to SARS-CoV-2 Selected from a Human Antibody Library Constructed Decades Ago

Min Qiang, Peixiang Ma, Yu Li, Hejun Liu, Adam Harding, Chenyu Min, Fulian Wang, Lili Liu, Meng Yuan, Qun Ji, Pingdong Tao, Xiaojie Shi, Zhean Li, Teng Li, Xian Wang, Yu Zhang, Nicholas C. Wu, Chang Chun D. Lee, Xueyong Zhu, Javier Gilbert-JaramilloChuyue Zhang, Abhishek Saxena, Xingxu Huang, Hou Wang, William James, Raymond A. Dwek, Ian A. Wilson, Guang Yang, Richard A. Lerner

Research output: Contribution to journalArticlepeer-review


Combinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, a combinatorial human antibody library constructed 20 years before the coronavirus disease 2019 (COVID-19) pandemic is used to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus. Compared to neutralizing antibodies from COVID-19 patients with generally low somatic hypermutation (SHM), these three antibodies contain over 13–22 SHMs, many of which are involved in specific interactions in their crystal structures with SARS-CoV-2 spike receptor binding domain. The identification of these somatically mutated antibodies in a pre-pandemic library raises intriguing questions about the origin and evolution of these antibodies with respect to their reactivity with SARS-CoV-2.

Original languageEnglish (US)
Article number2102181
JournalAdvanced Science
Issue number1
StatePublished - Jan 5 2022
Externally publishedYes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)


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