DOI: 10.1016/j.scib.2020.08.035
论文题名: Cyclovirobuxine D inhibits dengue virus replication by impeding the complete autophagy in a cholesterol-dependent manner
作者: Wang K. ; Zhang J. ; Ge Y. ; Dong C. ; Dai J.
刊名: Science Bulletin
ISSN: 20959273
出版年: 2021
卷: 66, 期: 3 起始页码: 284
结束页码: 296
语种: 英语
中文关键词: 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
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 Citation statistics:
资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/170424
Appears in Collections: 气候变化与战略
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作者单位: Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, 215123, China
Recommended Citation:
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]. Science Bulletin,2021-01-01,66(3)