Designed variants of ACE2-Fc that decouple anti-SARS-CoV-2 activities from unwanted cardiovascular effects.
Int J Biol Macromol
; 165(Pt B): 1626-1633, 2020 Dec 15.
Article
in English
| MEDLINE | ID: covidwho-866724
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.
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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
Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for SARS-CoV-2, and recombinant ACE2 decoys are being evaluated as new antiviral therapies. We designed and tested an antibody-like ACE2-Fc fusion protein, which has the benefit of long pharmacological half-life and the potential to facilitate immune clearance of the virus. Out of a concern that the intrinsic catalytic activity of ACE2 may unintentionally alter the balance of its hormonal substrates and cause adverse cardiovascular effects in treatment, we performed a mutagenesis screening for inactivating the enzyme. Three mutants, R273A, H378A and E402A, completely lost their enzymatic activity for either surrogate or physiological substrates. All of them remained capable of binding SARS-CoV-2 and could suppress the transduction of a pseudotyped virus in cell culture. This study established new ACE2-Fc candidates as antiviral treatment for SARS-CoV-2 without potentially harmful side effects from ACE2's catalytic actions toward its vasoactive substrates.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Recombinant Fusion Proteins
/
Immunoglobulin Fc Fragments
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
COVID-19
/
COVID-19 Drug Treatment
Type of study:
Experimental Studies
Topics:
Variants
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
Int J Biol Macromol
Year:
2020
Document Type:
Article
Affiliation country:
J.ijbiomac.2020.10.120
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