期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 50, 页码 32105-32113出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2012197117
关键词
SARS-CoV-2; interferon; virus entry; COVID-19; innate immunity
资金
- NIH Digestive Diseases Research Core Center Grants [P30 DK052574, R00 AI135031, R01 AI150796]
- COVID-19 Fast Grants Funding
- Harvard Virology Program, NIH training Grant [T32 AI07245]
- NIH [75N93019C00062, R01 AI127828]
- Defense Advanced Research Project Agency [HR001117S0019]
- Washington University School of Medicine in St. Louis
- Helen Hay Whitney Foundation postdoctoral fellowship
- Biotechnology and Biological Sciences Research Council [BB/L001942/1]
- [R37 AI059371]
- [GM130386]
- BBSRC [BB/L001942/1] Funding Source: UKRI
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-SAR-S-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.
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