Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2
Résumé
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 IC50 of 0.101 mu g mL-1 (6.2 nM). A crystal structure of the DL4-RBD complex at 1.75-angstrom 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.
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Li et al-2022-Isolation, characterization, and structure-based engineering of a neutralizing.pdf (1.63 Mo)
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Li_ScienceDirect_files_20Jul2022_08-23-10.658.zip (2.61 Mo)
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