- Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion.
Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion.
Proceedings of the National Academy of Sciences of the United States of America (2020-11-27)
Ruochen Zang, James Brett Case, Eylan Yutuc, Xiucui Ma, Sheng Shen, Maria Florencia Gomez Castro, Zhuoming Liu, Qiru Zeng, Haiyan Zhao, Juhee Son, Paul W Rothlauf, Alex J B Kreutzberger, Gaopeng Hou, Hu Zhang, Sayantan Bose, Xin Wang, Michael D Vahey, Kartik Mani, William J Griffiths, Tom Kirchhausen, Daved H Fremont, Haitao Guo, Abhinav Diwan, Yuqin Wang, Michael S Diamond, Sean P J Whelan, Siyuan Ding
PMID33239446
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.