Open AccessCholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion
Author(s) -
Ruochen Zang,
James Brett Case,
Eylan Yutuc,
Xiucui Ma,
Sheng Shen,
María Florencia Gómez 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,
Xueying Wang,
Michael S. Diamond,
Sean P. J. Whelan,
Siyuan Ding
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2012197117
Subject(s) - vesicular stomatitis virus , lipid bilayer fusion , viral envelope , endosome , biology , virology , viral replication , viral entry , coronavirus , interferon , microbiology and biotechnology , chemistry , virus , covid-19 , intracellular , medicine , pathology , infectious disease (medical specialty) , disease
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.