High-content screening of diterpenoids from Isodon species as autophagy modulators and the functional study of their antiviral activities

doi:10.1007/s10565-021-09580-6

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	High-content screening of diterpenoids from Isodon species as autophagy modulators and the functional study of their antiviral activities
	Huang,Lihong ; Fu,Qiang ; Dai,Jia-Meng ; Yan,Bing-Chao ; Wang,Dawei ; Puno,Pema-Tenzin ; Yue,Jianbo
	2021
发表期刊	CELL BIOLOGY AND TOXICOLOGY
ISSN	0742-2091
卷号	37 期号:5 页码:695-713
摘要	Autophagy is a conserved lysosomal degradation process, and abnormal autophagy has been associated with various pathological processes, e.g., neurodegeneration, cancer, and pathogen infection. Small chemical modulators of autophagy show the potential to treat autophagy-associated diseases. Diterpenoids, nature products found in various plants, exhibit a wide range of bioactivity, and we have recently isolated and characterized over 150 diterpenoids from Isodon species distributed in China. Here, we applied a high-content fluorescence imaging-based assay to assess these diterpenoids' ability to affect autophagic flux in HeLa cells. We found that enanderinanin J, an ent-kauranoid dimer, is an autophagy inhibitor, manifested by its ability to increase lysosomal pH and inhibit the fusion between autophagosomes and lysosomes. Autophagy has been shown to be either positively or negatively involved in the life cycle of Zika virus (ZIKV), Japanese encephalitis virus (JEV), Dengue virus (DENV), and enterovirus-A71 (EV-A71). We found that enanderinanin J significantly inhibited the infection of ZIKV, DENV, JEV, or EV-A71. Interestingly, although ATG5 knockdown inhibited ZIKV or JEV infection, enanderinanin J further inhibited the infection of ZIKV or JEV in ATG5-knockdown cells. Taken together, our data indicate that enanderinanin J inhibits autophagosome-lysosome fusion and is a potential antiviral agent.
关键词	Diterpenoids Autophagy Lysosome Autophagosome Enanderinanin J Dengue virus (DENV) Zika virus (ZIKV) Japanese encephalitis virus (JEV) Enterovirus-A71 (EV-A71)
DOI	10.1007/s10565-021-09580-6
WOS记录号	WOS:000610495300001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/73368
专题	中国科学院昆明植物研究所
作者单位	1.City Univ Hong Kong, Shenzhen Res Inst, Shenzhen, Peoples R China 2.City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Peoples R China 3.Xinjiang Agr Univ, Coll Vet Med, Urumqi, Peoples R China 4.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Peoples R China 5.Yunnan Key Lab Nat Med Chem, Kunming 650201, Peoples R China 6.City Univ Hong Kong, Chengdu Res Inst, Chengdu, Peoples R China
推荐引用方式 GB/T 7714	Huang,Lihong,Fu,Qiang,Dai,Jia-Meng,et al. High-content screening of diterpenoids from Isodon species as autophagy modulators and the functional study of their antiviral activities[J]. CELL BIOLOGY AND TOXICOLOGY,2021,37(5):695-713.
APA	Huang,Lihong.,Fu,Qiang.,Dai,Jia-Meng.,Yan,Bing-Chao.,Wang,Dawei.,...&Yue,Jianbo.(2021).High-content screening of diterpenoids from Isodon species as autophagy modulators and the functional study of their antiviral activities.CELL BIOLOGY AND TOXICOLOGY,37(5),695-713.
MLA	Huang,Lihong,et al."High-content screening of diterpenoids from Isodon species as autophagy modulators and the functional study of their antiviral activities".CELL BIOLOGY AND TOXICOLOGY 37.5(2021):695-713.

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