期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 27, 期 9, 页码 846-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41594-020-0469-6
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资金
- Rosalind Franklin Institute, EPSRC [EP/S025243/1]
- Wellcome Trust [100209/Z/12/Z, 101122/Z/13/Z]
- Cancer Research UK grants [C20724/A14414, C20724/A26752]
- National Secretariat of Education (Senescyt-IFTH), Ecuador
- UK Medical Research Council [MR/N00065X/1]
- Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China [2018-I2M-2-002]
- EPA Cephalosporin Fund
- Townsend-Jeantet Charitable Trust [1011770]
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/M011224/1]
- Wellcome Trust [101122/Z/13/Z, 100209/Z/12/Z] Funding Source: Wellcome Trust
- MRC [MR/N00065X/1] Funding Source: UKRI
Two nanobodies that bind SARS-CoV-2 spike RBD are shown to block interaction with receptor ACE2 and thus neutralize the virus, and have an additive effect with antibody CR3022. The SARS-CoV-2 virus is more transmissible than previous coronaviruses and causes a more serious illness than influenza. The SARS-CoV-2 receptor binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell. Using a naive llama single-domain antibody library and PCR-based maturation, we have produced two closely related nanobodies, H11-D4 and H11-H4, that bind RBD (K(D)of 39 and 12 nM, respectively) and block its interaction with ACE2. Single-particle cryo-EM revealed that both nanobodies bind to all three RBDs in the spike trimer. Crystal structures of each nanobody-RBD complex revealed how both nanobodies recognize the same epitope, which partly overlaps with the ACE2 binding surface, explaining the blocking of the RBD-ACE2 interaction. Nanobody-Fc fusions showed neutralizing activity against SARS-CoV-2 (4-6 nM for H11-H4, 18 nM for H11-D4) and additive neutralization with the SARS-CoV-1/2 antibody CR3022.
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