SARS-CoV-2 receptor binding domain fusion protein efficiently neutralizes virus infection.
PLoS Pathog
; 17(12): e1010175, 2021 12.
Article
in English
| MEDLINE | ID: covidwho-1592244
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.
See 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.
See preprint
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Currently, as dangerous mutations emerge, there is an increased demand for specific treatments for SARS-CoV-2 infected patients. The spike glycoprotein on the virus envelope binds to the angiotensin converting enzyme 2 (ACE2) on host cells through its receptor binding domain (RBD) to mediate virus entry. Thus, blocking this interaction may inhibit viral entry and consequently stop infection. Here, we generated fusion proteins composed of the extracellular portions of ACE2 and RBD fused to the Fc portion of human IgG1 (ACE2-Ig and RBD-Ig, respectively). We demonstrate that ACE2-Ig is enzymatically active and that it can be recognized by the SARS-CoV-2 RBD, independently of its enzymatic activity. We further show that RBD-Ig efficiently inhibits in-vivo SARS-CoV-2 infection better than ACE2-Ig. Mechanistically, we show that anti-spike antibody generation, ACE2 enzymatic activity, and ACE2 surface expression were not affected by RBD-Ig. Finally, we show that RBD-Ig is more efficient than ACE2-Ig at neutralizing high virus titers. We thus propose that RBD-Ig physically blocks virus infection by binding to ACE2 and that RBD-Ig should be used for the treatment of SARS-CoV-2-infected patients.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Recombinant Fusion Proteins
/
Immunoglobulin G
/
Immunoglobulin Fc Fragments
/
Protein Domains
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
PLoS Pathog
Year:
2021
Document Type:
Article
Affiliation country:
Journal.ppat.1010175
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