Accelerating PERx reaction enables covalent nanobodies for potent neutralization of SARS-CoV-2 and variants.
Chem
; 8(10): 2766-2783, 2022 Oct 13.
Article
in English
| MEDLINE | ID: covidwho-1936147
ABSTRACT
The long-lasting COVID-19 pandemic and increasing SARS-CoV-2 variants demand effective drugs for prophylactics and treatment. Protein-based biologics offer high specificity, yet their noncovalent interactions often lead to drug dissociation and incomplete inhibition. Here, we have developed covalent nanobodies capable of binding with SARS-CoV-2 irreversibly via a proximity-enabled reactive therapeutic (PERx) mechanism. A latent bioreactive amino acid (FFY) was designed and genetically encoded into nanobodies to accelerate the PERx reaction rate. Compared with the noncovalent wild-type nanobody, the FFY-incorporated covalent nanobodies neutralized both wild-type SARS-CoV-2 and its Alpha, Delta, Epsilon, Lambda, and Omicron variants with drastically higher potency. This PERx-enabled covalent-nanobody strategy and the related insights into increased potency can be valuable to developing effective therapeutics for various viral infections.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Topics:
Long Covid
/
Variants
Language:
English
Journal:
Chem
Year:
2022
Document Type:
Article
Affiliation country:
J.chempr.2022.07.012
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