Atranorin inhibits Zika virus infection in human glioblastoma cell line SNB-19 via targeting Zika virus envelope protein
文献类型：期刊论文
| 作者 | Huang, Guan-gen2,3; Wang, Hao-yu1,3; Wang, Xiao-han1,3; Yang, Tao1,3; Zhang, Xiao-meng3; Feng, Chun-lan3; Zhao, Wei-min; Tang, Wei1,2,3
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| 刊名 | PHYTOMEDICINE
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| 出版日期 | 2024-03-01 |
| 卷号 | 125页码:11 |
| 关键词 | Zika virus SNB-19 cells Atranorin Envelope protein Entry stage Antiviral drugs |
| ISSN号 | 0944-7113 |
| DOI | 10.1016/j.phymed.2024.155343 |
| 通讯作者 | Tang, Wei(tangwei@simm.ac.cn) |
| 英文摘要 | Background: Zika virus (ZIKV) is a single-stranded RNA flavivirus transmitted by mosquitoes. Its infection is associated with neurological complications such as neonatal microcephaly and adult Guillain-Barre ' syndrome, posing a serious threat to the health of people worldwide. Therefore, there is an urgent need to develop effective anti-ZIKV drugs. Atranorin is a lichen secondary metabolite with a wide range of biological activities, including anti-inflammatory, antibacterial and antioxidant, etc. However, the antiviral activity of atranorin and underlying mechanism has not been fully elucidated. Purpose: We aimed to determine the anti-ZIKV activity of atranorin in human glioma cell line SNB-19 and investigate the potential mechanism from the perspective of viral life cycle and the host cell functions. Methods: We first established ZIKV-infected human glioma cells (SNB-19) model and used Western Blot, RTqPCR, immunofluorescence, fluorescence-activated cell sorting (FACS) and plaque assay to evaluate the antiZIKV activity of atranorin. Then we assessed the regulation effect of atranorin on ZIKV induced IFN signal pathway activation by RT-qPCR. Afterward, we introduced time-of-addition assay, viral adsorption assay, viral internalization assay and transferrin uptake assay to define which step of ZIKV lifecycle is influenced by atranorin. Finally, we performed virus infectivity assay, molecular docking and thermal shift assay to uncover the target protein of atranorin on ZIKV. Results: Our study showed that atranorin could protect SNB-19 cells from ZIKV infection, as evidenced by inhibited viral protein expression and progeny virus yield. Meanwhile, atranorin attenuated the activation of IFN signal pathway and downstream inflammatory response that induced by ZIKV infection. The results of time-ofaddition assay indicated that atranorin acted primarily by disturbing the viral entry process. After ruling out the effect of atranorin on AXL receptor tyrosine kinase (AXL) dependent virus adsorption and clathrin-mediated endocytosis, we confirmed that atranorin directly targeted the viral envelope protein and lowered ZIKV infectivity by thermal shift assay and virus infectivity assay respectively. Conclusion: We found atranorin inhibits ZIKV infection in SNB-19 cells via targeting ZIKV envelope protein. Our study provided an experimental basis for the further development of atranorin and a reference for antiviral drug discovery from natural resources. |
| WOS关键词 | BIOLOGY |
| 资助项目 | National Key R&D Program of China[2021YFC2300700] |
| WOS研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001181145100001 |
| 出版者 | ELSEVIER GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/310190]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Tang, Wei |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Huang, Guan-gen,Wang, Hao-yu,Wang, Xiao-han,et al. Atranorin inhibits Zika virus infection in human glioblastoma cell line SNB-19 via targeting Zika virus envelope protein[J]. PHYTOMEDICINE,2024,125:11. |
| APA | Huang, Guan-gen.,Wang, Hao-yu.,Wang, Xiao-han.,Yang, Tao.,Zhang, Xiao-meng.,...&Tang, Wei.(2024).Atranorin inhibits Zika virus infection in human glioblastoma cell line SNB-19 via targeting Zika virus envelope protein.PHYTOMEDICINE,125,11. |
| MLA | Huang, Guan-gen,et al."Atranorin inhibits Zika virus infection in human glioblastoma cell line SNB-19 via targeting Zika virus envelope protein".PHYTOMEDICINE 125(2024):11. |
入库方式： OAI收割
来源：上海药物研究所
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