胆固醇 25-羟化酶通过阻断膜融合来抑制 SARS-CoV-2 的复制。
Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion.
机构信息
Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 266100 Qingdao, China.
出版信息
Proc Natl Acad Sci U S A. 2020 Dec 15;117(50):32105-32113. doi: 10.1073/pnas.2012197117. Epub 2020 Nov 25.
Cholesterol 25-hydroxylase () 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.
胆固醇 25-羟化酶（）是一种干扰素（IFN）刺激基因，对广泛的包膜病毒具有广泛的抗病毒活性。在这里，我们使用针对水疱性口炎病毒（VSV）-SARS-CoV 和 VSV-SARS-CoV-2 嵌合病毒的 IFN 刺激基因筛选，鉴定出 CH25H 和其酶产物 25-羟胆固醇（25HC）是 SARS-CoV-2 复制的有效抑制剂。内化的 25HC 积累在晚期内体中，并通过阻止胆固醇外排潜在地限制 SARS-CoV-2 刺突蛋白催化的膜融合。我们的结果强调了 25HC 的一种可能的抗病毒机制，并为其治疗开发提供了分子基础。
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