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

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Author Name

Ruochen Zang

Published 3 Projects

Microbiology

James Brett Case

Maria Florencia Gomez Castro

Published 2 Projects

Microbiology

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Zhuoming Liu

Qiru Zeng

Published 4 Projects

Microbiology

Haiyan Zhao

Published 4 Projects

Microbiology

Juhee Son

Published 2 Projects

Microbiology

Paul W Rothlauf

Gaopeng Hou

Published 2 Projects

Microbiology

Sayantan Bose

Published 1 Project

Microbiology

Xin Wang

Published 4 Projects

Microbiology Biochemistry

Michael D. Vahey

Published 1 Project

Microbiology

Tomas Kirchhausen

Published 1 Project

Microbiology

Daved H Fremont

Published 4 Projects

Immunology Microbiology

Michael Diamond

Sean P. J. Whelan

Siyuan Ding

Published 4 Projects

Microbiology

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Cholesterol 25-hydroxylase (CH25H) is an interferon-stimulated gene (ISG) that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an ISG screen against VSV-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of virus replication. Mechanistically, internalized 25HC accumulates in the late endosomes and blocks cholesterol export, thereby restricting SARS-CoV-2 spike protein catalyzed membrane fusion. Our results highlight a unique antiviral mechanism of 25HC and provide the molecular basis for its possible therapeutic development. ### Competing Interest Statement M.S.D. is a consultant for Inbios, Eli Lilly, Vir Biotechnology, NGM Biopharmaceuticals, and Emergent BioSolutions and on the Scientific Advisory Board of Moderna. The Diamond laboratory at Washington University School of Medicine has received sponsored research agreements from Moderna. Invention disclosure filed with Washington University in St. Louis for the recombinant VSV-SARS-CoV-2 used herein.

Microbiology
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