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Article Dans Une Revue International Journal of Biological Macromolecules Année : 2022

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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Dates et versions

hal-03711033 , version 1 (20-07-2022)

Identifiants

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Tingting Li, Bingjie Zhou, Yaning Li, Suqiong Huang, Zhipu Luo, et al.. Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2. International Journal of Biological Macromolecules, 2022, 209, pp.1379-1388. ⟨10.1016/j.ijbiomac.2022.04.096⟩. ⟨hal-03711033⟩
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