Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33239446.
- Also identified by DOI 10.1073/pnas.2012197117 and PMC identifier 7749331.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Cholesterol 25-hydroxylase (<i>CH25H</i>) 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.
Medical subject headings
- Endosomes
- Hydroxycholesterols
- Spike Glycoprotein, Coronavirus
- COVID-19 Drug Treatment