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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.
Affiliation
  • Zang R; Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
  • Case JB; Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 266100 Qingdao, China.
  • Yutuc E; Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
  • Ma X; Swansea University Medical School, SA2 8PP Swansea, United Kingdom.
  • Shen S; Center for Cardiovascular Research and Division of Cardiology, Department of Internal Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63111.
  • Gomez Castro MF; John Cochran VA Medical Center, St. Louis, MO 63106.
  • Liu Z; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202.
  • Zeng Q; Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
  • Zhao H; Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
  • Son J; Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
  • Rothlauf PW; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
  • Kreutzberger AJB; Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
  • Hou G; Program in Molecular Cell Biology, Washington University School of Medicine, St. Louis, MO 63110.
  • Zhang H; Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
  • Bose S; Program in Virology, Harvard Medical School, Boston, MA 02115.
  • Wang X; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
  • Vahey MD; Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
  • Mani K; Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
  • Griffiths WJ; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202.
  • Kirchhausen T; Autonomous Therapeutics, Inc., New York, NY 10013.
  • Fremont DH; Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 266100 Qingdao, China.
  • Guo H; Department of Biomedical Engineering, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO 63110.
  • Diwan A; Center for Cardiovascular Research and Division of Cardiology, Department of Internal Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63111.
  • Wang Y; John Cochran VA Medical Center, St. Louis, MO 63106.
  • Diamond MS; Swansea University Medical School, SA2 8PP Swansea, United Kingdom.
  • Whelan SPJ; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
  • Ding S; Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A ; 117(50): 32105-32113, 2020 12 15.
Article in En | MEDLINE | ID: mdl-33239446
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Endosomes / Spike Glycoprotein, Coronavirus / COVID-19 Drug Treatment / Hydroxycholesterols Limits: Humans Language: En Journal: Proc Natl Acad Sci U S A Year: 2020 Document type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Endosomes / Spike Glycoprotein, Coronavirus / COVID-19 Drug Treatment / Hydroxycholesterols Limits: Humans Language: En Journal: Proc Natl Acad Sci U S A Year: 2020 Document type: Article