Ultrapotent miniproteins targeting the SARS-CoV-2 receptor-binding domain protect against infection and disease.
Cell Host Microbe
; 29(7): 1151-1161.e5, 2021 07 14.
Article
in English
| MEDLINE | ID: covidwho-1283986
ABSTRACT
Despite the introduction of public health measures and spike protein-based vaccines to mitigate the COVID-19 pandemic, SARS-CoV-2 infections and deaths continue to have a global impact. Previously, we used a structural design approach to develop picomolar range miniproteins targeting the SARS-CoV-2 spike receptor-binding domain. Here, we investigated the capacity of modified versions of one lead miniprotein, LCB1, to protect against SARS-CoV-2-mediated lung disease in mice. Systemic administration of LCB1-Fc reduced viral burden, diminished immune cell infiltration and inflammation, and completely prevented lung disease and pathology. A single intranasal dose of LCB1v1.3 reduced SARS-CoV-2 infection in the lung when given as many as 5 days before or 2 days after virus inoculation. Importantly, LCB1v1.3 protected in vivo against a historical strain (WA1/2020), an emerging B.1.1.7 strain, and a strain encoding key E484K and N501Y spike protein substitutions. These data support development of LCB1v1.3 for prevention or treatment of SARS-CoV-2 infection.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Protein Binding
/
COVID-19 Vaccines
/
SARS-CoV-2
/
COVID-19
Type of study:
Experimental Studies
Topics:
Vaccines
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Journal:
Cell Host Microbe
Journal subject:
Microbiology
Year:
2021
Document Type:
Article
Affiliation country:
J.chom.2021.06.008
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