Versatile and multivalent nanobodies efficiently neutralize SARS-CoV-2

Author:

Xiang Yufei1ORCID,Nambulli Sham23ORCID,Xiao Zhengyun1ORCID,Liu Heng4ORCID,Sang Zhe15ORCID,Duprex W. Paul23ORCID,Schneidman-Duhovny Dina6ORCID,Zhang Cheng4ORCID,Shi Yi15ORCID

Affiliation:

1. Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.

2. Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.

3. Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA.

4. Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.

5. University of Pittsburgh–Carnegie Mellon University Program in Computational Biology, Pittsburgh, PA, USA.

6. School of Computer Science and Engineering, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.

Abstract

Nanobodies that neutralize Monoclonal antibodies that bind to the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show therapeutic promise but must be produced in mammalian cells and need to be delivered intravenously. By contrast, single-domain antibodies called nanobodies can be produced in bacteria or yeast, and their stability may enable aerosol delivery. Two papers now report nanobodies that bind tightly to spike and efficiently neutralize SARS-CoV-2 in cells. Schoof et al. screened a yeast surface display of synthetic nanobodies and Xiang et al. screened anti-spike nanobodies produced by a llama. Both groups identified highly potent nanobodies that lock the spike protein in an inactive conformation. Multivalent constructs of selected nanobodies achieved even more potent neutralization. Science , this issue p. 1473 , p. 1479

Funder

National Institutes of Health

University of Pittsburgh

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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