期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-19204-y
关键词
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资金
- EU
- Swedish Research Council [2018-02381, 2017-6702, 2018-3808, 2018-03843]
- Knut and Alice Wallenberg Foundation
- Vinnova [2018-03843] Funding Source: Vinnova
- Swedish Research Council [2018-03843, 2018-02381] Funding Source: Swedish Research Council
The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Therapeutic neutralizing antibodies constitute a key short-to-medium term approach to tackle COVID-19. However, traditional antibody production is hampered by long development times and costly production. Here, we report the rapid isolation and characterization of nanobodies from a synthetic library, known as sybodies (Sb), that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Several binders with low nanomolar affinities and efficient neutralization activity were identified of which Sb23 displayed high affinity and neutralized pseudovirus with an IC50 of 0.6 mu g/ml. A cryo-EM structure of the spike bound to Sb23 showed that Sb23 binds competitively in the ACE2 binding site. Furthermore, the cryo-EM reconstruction revealed an unusual conformation of the spike where two RBDs are in the 'up' ACE2-binding conformation. The combined approach represents an alternative, fast workflow to select binders with neutralizing activity against newly emerging viruses. Here, the authors isolate several nanobodies from a synthetic library that bind the receptor-binding domain (RBD) of SARS-CoV-2 spike protein (S) and neutralize S pseudotyped viruses. Cryo-EM structure of Spike with one nanobody and further biophysical analysis shows competition with ACE2 binding.
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