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

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dc.contributor.authorZang, Ruochen
dc.contributor.authorCase, James Brett
dc.contributor.authorYutuc, Eylan
dc.contributor.authorMa, Xiucui
dc.contributor.authorShen, Sheng
dc.contributor.authorGomez Castro, Maria Florencia
dc.contributor.authorLiu, Zhuoming
dc.contributor.authorZeng, Qiru
dc.contributor.authorZhao, Haiyan
dc.contributor.authorSon, Juhee
dc.contributor.authorRothlauf, Paul W.
dc.contributor.authorKreutzberger, Alex J. B.
dc.contributor.authorHou, Gaopeng
dc.contributor.authorZhang, Hu
dc.contributor.authorBose, Sayantan
dc.contributor.authorWang, Xin
dc.contributor.authorVahey, Michael D.
dc.contributor.authorMani, Kartik
dc.contributor.authorGriffiths, William J.
dc.contributor.authorKirchhausen, Tom
dc.contributor.authorFremont, Daved H.
dc.contributor.authorGuo, Haitao
dc.contributor.authorDiwan, Abhinav
dc.contributor.authorWang, Yuqin
dc.contributor.authorDiamond, Michael S.
dc.contributor.authorWhelan, Sean P. J.
dc.contributor.authorDing, Siyuan
dc.contributor.departmentMicrobiology and Immunology, School of Medicineen_US
dc.date.accessioned2021-04-15T20:10:38Z
dc.date.available2021-04-15T20:10:38Z
dc.date.issued2020-12
dc.description.abstractCholesterol 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.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationZang, R., Case, J. B., Yutuc, E., Ma, X., Shen, S., Castro, M. F. G., ... & Ding, S. (2020). Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion. Proceedings of the National Academy of Sciences, 117(50), 32105-32113. https://doi.org/10.1073/pnas.2012197117en_US
dc.identifier.urihttps://hdl.handle.net/1805/25653
dc.language.isoenen_US
dc.publisherNASen_US
dc.relation.isversionof10.1073/pnas.2012197117en_US
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.sourcePublisheren_US
dc.subjectSARS-CoV-2en_US
dc.subjectinterferonen_US
dc.subjectvirus entryen_US
dc.subjectCOVID-19en_US
dc.titleCholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusionen_US
dc.typeArticleen_US
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