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

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-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.

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Zang, 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.2012197117
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Proceedings of the National Academy of Sciences
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