A high-affinity RBD-targeting nanobody improves fusion partner's potency against SARS-CoV-2.
PLoS Pathog
; 17(3): e1009328, 2021 03.
Article
in English
| MEDLINE | ID: covidwho-1115314
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
A key step to the SARS-CoV-2 infection is the attachment of its Spike receptor-binding domain (S RBD) to the host receptor ACE2. Considerable research has been devoted to the development of neutralizing antibodies, including llama-derived single-chain nanobodies, to target the receptor-binding motif (RBM) and to block ACE2-RBD binding. Simple and effective strategies to increase potency are desirable for such studies when antibodies are only modestly effective. Here, we identify and characterize a high-affinity synthetic nanobody (sybody, SR31) as a fusion partner to improve the potency of RBM-antibodies. Crystallographic studies reveal that SR31 binds to RBD at a conserved and 'greasy' site distal to RBM. Although SR31 distorts RBD at the interface, it does not perturb the RBM conformation, hence displaying no neutralizing activities itself. However, fusing SR31 to two modestly neutralizing sybodies dramatically increases their affinity for RBD and neutralization activity against SARS-CoV-2 pseudovirus. Our work presents a tool protein and an efficient strategy to improve nanobody potency.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antibodies, Neutralizing
/
Single-Domain Antibodies
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
Antibodies, Viral
Limits:
Humans
Language:
English
Journal:
PLoS Pathog
Year:
2021
Document Type:
Article
Affiliation country:
Journal.ppat.1009328
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