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Updated: Nov 28, 2025
05:23
Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
Published on: December 23, 2020
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Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion
Ruochen Zang1,2, James Brett Case3, Eylan Yutuc4
1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Summary
Cholesterol 25-hydroxylase (CH25H) and its product 25-hydroxycholesterol (25HC) effectively inhibit SARS-CoV-2 replication. This discovery offers a potential therapeutic strategy by targeting viral entry mechanisms.
Area of Science:
- Virology
- Immunology
- Biochemistry
Background:
- Cholesterol 25-hydroxylase (CH25H) is an interferon-stimulated gene with known broad-spectrum antiviral properties against enveloped viruses.
- SARS-CoV-2, the virus responsible for COVID-19, poses a significant global health challenge, necessitating the identification of novel antiviral targets and therapeutics.
Purpose of the Study:
- To identify interferon-stimulated genes that inhibit SARS-CoV-2 replication.
- To investigate the antiviral mechanism of CH25H and its product, 25-hydroxycholesterol (25HC), against SARS-CoV-2.
Main Methods:
- Conducted an interferon-stimulated gene screen using vesicular stomatitis virus (VSV)-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses.
- Analyzed the accumulation and localization of internalized 25HC within host cells.
- Investigated the effect of 25HC on SARS-CoV-2 spike protein-mediated membrane fusion.
Main Results:
- CH25H and 25HC were identified as potent inhibitors of SARS-CoV-2 replication.
- Internalized 25HC accumulates in late endosomes.
- 25HC potentially restricts viral entry by blocking cholesterol export, thereby inhibiting SARS-CoV-2 spike protein-mediated membrane fusion.
Conclusions:
- CH25H and its product 25HC represent promising therapeutic candidates against SARS-CoV-2.
- The findings elucidate a potential antiviral mechanism of 25HC involving the disruption of host cell cholesterol homeostasis and viral membrane fusion.
- This study provides a molecular basis for the therapeutic development of 25HC against SARS-CoV-2 and potentially other enveloped viruses.
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