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HGNC Genes

SARS-CoV-2 proteins

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    Cholesterol 25-hydroxylase HGNC suppresses SARS-CoV-2 replication by blocking membrane fusion

    Authors: Siyuan Ding; Ruochen Zang; James Brett Case; Maria Florencia Gomez Castro; Zhuoming Liu; Qiru Zeng; Haiyan Zhao; Juhee Son; Paul W. Rothlauf; Gaopeng Hou; Sayantan Bose; Xin Wang; Michael D Vahey; Tom Kirchhausen; Daved H. Fremont; Michael S. Diamond; Sean P. J. Whelan

    doi:10.1101/2020.06.08.141077 Date: 2020-06-09 Source: bioRxiv

    Cholesterol 25-hydroxylase HGNC ( CH25H HGNC) 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 MESHD chimeric viruses, we identified CH25H HGNC 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 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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MeSH Disease
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