A broad neutralizing nanobody against SARS-CoV-2 engineered from an approved drug.
Cell Death Dis
; 15(6): 458, 2024 Jun 28.
Article
in En
| MEDLINE
| ID: mdl-38937437
ABSTRACT
SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain. Blocking this interaction has been proven to be an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody named VHH60, which was directly produced from an engineering nanobody library based on a commercialized nanobody within a very short period. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein at S351, S470-471and S493-494 as determined by structural analysis, with an affinity of 2.56 nM. It inhibits infections of both ancestral SARS-CoV-2 strain and pseudotyped viruses harboring SARS-CoV-2 wildtype, key mutations or variants at the nanomolar level. Furthermore, VHH60 suppressed SARS-CoV-2 infection and propagation 50-fold better and protected mice from death for twice as long as the control group after SARS-CoV-2 nasal infections in vivo. Therefore, VHH60 is not only a powerful nanobody with a promising profile for disease control but also provides evidence for a highly effective and rapid approach to generating therapeutic nanobodies.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antibodies, Neutralizing
/
Single-Domain Antibodies
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Spike Glycoprotein, Coronavirus
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Angiotensin-Converting Enzyme 2
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SARS-CoV-2
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COVID-19
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cell Death Dis
Year:
2024
Document type:
Article