Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion.
Proc Natl Acad Sci U S A
; 117(50): 32105-32113, 2020 12 15.
Article
in En
| MEDLINE
| ID: mdl-33239446
ABSTRACT
Cholesterol 25-hydroxylase (CH25H) is an interferon (IFN)-stimulated gene that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an IFN-stimulated gene screen against vesicular stomatitis virus (VSV)-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of SARS-CoV-2 replication. Internalized 25HC accumulates in the late endosomes and potentially restricts SARS-CoV-2 spike protein catalyzed membrane fusion via blockade of cholesterol export. Our results highlight one of the possible antiviral mechanisms of 25HC and provide the molecular basis for its therapeutic development.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endosomes
/
Spike Glycoprotein, Coronavirus
/
COVID-19 Drug Treatment
/
Hydroxycholesterols
Limits:
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2020
Document type:
Article