Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion
- Zang, Ruochen
- Case, James Brett
- Yutuc, Eylan
- Ma, Xiucui
- Shen, Sheng
- Gomez Castro, Maria Florencia
- Liu, Zhuoming
- Zeng, Qiru
- Zhao, Haiyan
- Son, Juhee
- Rothlauf, Paul W.
- Kreutzberger, Alex J. B.
- Hou, Gaopeng
- Zhang, Hu
- Bose, Sayantan
- Wang, Xin
- Vahey, Michael D.
- Mani, Kartik
- Griffiths, William J.
- Kirchhausen, Tom
- Fremont, Daved H.
- Guo, Haitao
- Diwan, Abhinav
- Wang, Yuqin
- Diamond, Michael S.
- Whelan, Sean P. J.
- Ding, Siyuan
Publication date
December 2020
DOI Publisher
Proceedings of the National Academy of SciencesAbstract
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
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