Disruption of disulfides within RBD of SARS-CoV-2 spike protein prevents fusion and represents a target for viral entry inhibition by registered drugs.
FASEB J
; 35(6): e21651, 2021 06.
Article
in English
| MEDLINE | ID: covidwho-1388031
ABSTRACT
The SARS-CoV-2 pandemic imposed a large burden on health and society. Therapeutics targeting different components and processes of the viral infection replication cycle are being investigated, particularly to repurpose already approved drugs. Spike protein is an important target for both vaccines and therapeutics. Insights into the mechanisms of spike-ACE2 binding and cell fusion could support the identification of compounds with inhibitory effects. Here, we demonstrate that the integrity of disulfide bonds within the receptor-binding domain (RBD) plays an important role in the membrane fusion process although their disruption does not prevent binding of spike protein to ACE2. Several reducing agents and thiol-reactive compounds are able to inhibit viral entry. N-acetyl cysteine amide, L-ascorbic acid, JTT-705, and auranofin prevented syncytia formation, viral entry into cells, and infection in a mouse model, supporting disulfides of the RBD as a therapeutically relevant target.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Acetylcysteine
/
Ascorbic Acid
/
Sulfhydryl Compounds
/
Auranofin
/
Disulfides
/
Esters
/
Virus Internalization
/
Spike Glycoprotein, Coronavirus
/
Amides
/
SARS-CoV-2
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
FASEB J
Journal subject:
Biology
/
Physiology
Year:
2021
Document Type:
Article
Affiliation country:
FJ.202100560R
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