Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses.
Nat Commun
; 13(1): 7957, 2022 12 27.
Article
in English
| MEDLINE | ID: covidwho-2185833
ABSTRACT
As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with potency against diverse VOCs including Omicron subvariants BA.1, BA.2 and BA.4/5, SARS-CoV-1, and major sarbecoviruses. Crystal structure analysis of one representative nanobody, 3-2A2-4, discovers a highly conserved epitope located between the cryptic and the outer face of the receptor binding domain (RBD), distinctive from the receptor ACE2 binding site. Cryo-EM and biochemical evaluation reveal that 3-2A2-4 interferes structural alteration of RBD required for ACE2 binding. Passive delivery of 3-2A2-4 protects K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. Identification of these unique nanobodies will inform the development of next generation antibody therapies and design of pan-sarbecovirus vaccines.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Camelids, New World
/
Severe acute respiratory syndrome-related coronavirus
/
Single-Domain Antibodies
/
COVID-19
Type of study:
Experimental Studies
Topics:
Vaccines
/
Variants
Limits:
Animals
Language:
English
Journal:
Nat Commun
Journal subject:
Biology
/
Science
Year:
2022
Document Type:
Article
Affiliation country:
S41467-022-35642-2
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