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Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2.
- Source :
-
International Journal of Biological Macromolecules . Jun2022:Part A, Vol. 209, p1379-1388. 10p. - Publication Year :
- 2022
-
Abstract
- SARS-CoV-2 engages with human cells through the binding of its Spike receptor-binding domain (S-RBD) to the receptor ACE2. Molecular blocking of this engagement represents a proven strategy to treat COVID-19. Here, we report a single-chain antibody (nanobody, DL4) isolated from immunized alpaca with picomolar affinity to RBD. DL4 neutralizes SARS-CoV-2 pseudoviruses with an IC 50 of 0.101 μg mL−1 (6.2 nM). A crystal structure of the DL4-RBD complex at 1.75-Å resolution unveils the interaction detail and reveals a direct competition mechanism for DL4's ACE2-blocking and hence neutralizing activity. The structural information allows us to rationally design a mutant with higher potency. Our work adds diversity of neutralizing nanobodies against SARS-CoV-2 and should encourage protein engineering to improve antibody affinities in general. • Isolation of a neutralizing nanobody targeting RBD with picomolar affinity • The high-resolution structure of the nanobody-RBD complex reveals the neutralizing mechanism. • Structure-based engineering yielded improved potency. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01418130
- Volume :
- 209
- Database :
- Academic Search Index
- Journal :
- International Journal of Biological Macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 156914510
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2022.04.096