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.
Funder
RCUK | Biotechnology and Biological Sciences Research Council
HHS | NIH | National Institute of Allergy and Infectious Diseases
HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases
DOD | Defense Advanced Research Projects Agency
Helen Hay Whitney Foundation
Publisher
Proceedings of the National Academy of Sciences
Cited by
184 articles.
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