Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2.
Int J Biol Macromol
; 209(Pt A): 1379-1388, 2022 Jun 01.
Article
in English
| MEDLINE | ID: covidwho-1796724
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 IC50 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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Single-Domain Antibodies
/
SARS-CoV-2
Language:
English
Journal:
Int J Biol Macromol
Year:
2022
Document Type:
Article
Affiliation country:
J.ijbiomac.2022.04.096
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