气候变化领域集成服务门户(CCPortal): Cyclovirobuxine D inhibits dengue virus replication by impeding the complete autophagy in a cholesterol-dependent manner

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DOI	10.1016/j.scib.2020.08.035
	Cyclovirobuxine D inhibits dengue virus replication by impeding the complete autophagy in a cholesterol-dependent manner
	Wang K.; Zhang J.; Ge Y.; Dong C.; Dai J.
发表日期	2021
ISSN	20959273
起始页码	284
结束页码	296
卷号	66 期号:3
英文摘要	Dengue virus (DENV) is the most common mosquito-borne flavivirus, and it affects millions of people globally every year. Currently, there are no approved drugs for the treatment of dengue infection. By screening a natural product library, we identified a novel compound, cyclovirobuxine D (Cvb D), that displays anti-DENV activity. Cvb D inhibits DENV replication in vitro in a dose-dependent manner and protects suckling mice against lethal DENV infection. Mechanistically, Cvb D regulates the expression of genes related to the cellular cholesterol pathway. As a result, Cvb D increases cellular cholesterol synthesis and accumulation, activates mTOR, and inhibits viral-dependent autophagy. Cvb D does not suppress autophagy initiation but impedes the nuclear translocation of the lysosome transcription factor TFEB. In addition, Cvb D restricts the replication of other positive-strand RNA viruses such as Zika virus and Coxsackievirus B3. We speculate that Cvb D could be a broad-spectrum antiviral drug candidate for use against positive-strand RNA viruses that require autophagy for optimal replication. © 2020 Science China Press
关键词	Antiviral agent Autophagy Cholesterol pathway Cyclovirobuxine D Dengue virus mTOR
英文关键词	Cell death; Cholesterol; Mammals; RNA; Transcription; Anti-viral drugs; Broad spectrum; Cellular cholesterol; Dengue virus; Dose-dependent manner; Flavivirus; Natural product libraries; Nuclear translocations; Viruses
语种	英语
来源期刊	Science Bulletin
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/207590
作者单位	Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, 215123, China
推荐引用方式 GB/T 7714	Wang K.,Zhang J.,Ge Y.,et al. Cyclovirobuxine D inhibits dengue virus replication by impeding the complete autophagy in a cholesterol-dependent manner[J],2021,66(3).
APA	Wang K.,Zhang J.,Ge Y.,Dong C.,&Dai J..(2021).Cyclovirobuxine D inhibits dengue virus replication by impeding the complete autophagy in a cholesterol-dependent manner.Science Bulletin,66(3).
MLA	Wang K.,et al."Cyclovirobuxine D inhibits dengue virus replication by impeding the complete autophagy in a cholesterol-dependent manner".Science Bulletin 66.3(2021).