Author: Zang, Ruochen; Case, James Brett; Gomez Castro, Maria Florencia; Liu, Zhuoming; Zeng, Qiru; Zhao, Haiyan; Son, Juhee; Rothlauf, Paul W.; Hou, Gaopeng; Bose, Sayantan; Wang, Xin; Vahey, Michael D.; Kirchhausen, Tomas; Fremont, Daved H.; Diamond, Michael S.; Whelan, Sean P.J.; Ding, Siyuan
Title: Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion Cord-id: ecnued3k Document date: 2020_6_9
ID: ecnued3k
Snippet: Cholesterol 25-hydroxylase (CH25H) is an interferon-stimulated gene (ISG) that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an ISG screen against VSV-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of virus replication. Mechanistically, internalized 25HC accumulates in the late endosomes and blocks cholesterol export, thereby restricting SARS-CoV-2 spike protei
Document: Cholesterol 25-hydroxylase (CH25H) is an interferon-stimulated gene (ISG) that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an ISG screen against VSV-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of virus replication. Mechanistically, internalized 25HC accumulates in the late endosomes and blocks cholesterol export, thereby restricting SARS-CoV-2 spike protein catalyzed membrane fusion. Our results highlight a unique antiviral mechanism of 25HC and provide the molecular basis for its possible therapeutic development.
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