Journal article
Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion
Proceedings of the National Academy of Sciences - PNAS, Vol.117(50), pp.32105-32113
12/15/2020
DOI: 10.1073/pnas.2012197117
PMCID: PMC7749331
PMID: 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-SAR-S-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.
Details
- Title: Subtitle
- Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion
- Creators
- Ruochen Zeng - Washington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USAJames Brett Case - Washington University in St. LouisEylan Yutuc - Swansea UniversityXiucui Ma - Washington University in St. LouisSheng Sheng - Indiana UniversityMaria Florencia Gomez Castro - Washington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USAZhuoming Liu - Washington University in St. LouisQiru Zeng - Washington University in St. LouisHaiyan Zhao - Washington University in St. LouisJuhee Son - Washington University in St. LouisPaul W. Rothlauf - Washington University in St. LouisAlex J. B. Kreutzberger - Boston Children's HospitalGaopeng Hou - Washington University in St. LouisHu Zhang - Indiana University – Purdue University IndianapolisSayantan Bose - Autonomous HealthcareXin Wang - Ocean University of ChinaMichael D. Vahey - Washington University in St. LouisKartik Mani - Washington University in St. LouisWilliam J. Griffiths - Swansea UniversityTom Kirchhausen - Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USADaved H. Fremont - Washington University in St. LouisHaitao Guo - Indiana University – Purdue University IndianapolisAbhinav Diwan - Washington University in St. LouisYuqin Wang - Swansea UniversityMichael S. Diamond - Washington University in St. LouisSean P. J. Whelan - Washington University in St. LouisSiyuan Ding - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.117(50), pp.32105-32113
- Publisher
- Natl Acad Sciences
- DOI
- 10.1073/pnas.2012197117
- PMID
- 33239446
- PMCID
- PMC7749331
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Number of pages
- 9
- Grant note
- COVID-19 Fast Grants Funding HR001117S0019 / Defense Advanced Research Project Agency; United States Department of Defense; Defense Advanced Research Projects Agency (DARPA) T32 AI07245 / Harvard Virology Program, NIH training Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Helen Hay Whitney Foundation postdoctoral fellowship 75N93019C00062; R01 AI127828 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30 DK052574; R00 AI135031; R01 AI150796 / NIH Digestive Diseases Research Core Center Grants Washington University School of Medicine in St. Louis BB/L001942/1 / Biotechnology and Biological Sciences Research Council; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) BB/L001942/1 / BBSRC; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC)
- Language
- English
- Date published
- 12/15/2020
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984695677802771
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