Wikstroelide M potently inhibits HIV replication by targeting reverse transcriptase and integrase nuclear translocation
文献类型：期刊论文
| 作者 | Zhang X1,3; Huang SZ2; Gu WG4; Yang LM1; Chen H1; Zheng CB5; Zhao YX2; Wan David DC4; Zheng YT[*]1 |
| 刊名 | Chinese Journal of Natural Medicines
 |
| 出版日期 | 2014 |
| 卷号 | 12期号:3页码:186-193 |
| 关键词 | Wikstroelide M Daphnane diterpene Daphne acutiloba Rehder HIV Reverse trascriptase integrase Nuclear translocation Lens epithelium-derived growth factor (LEDGF/p75) Molecular docking |
| 通讯作者 | zhengyt@mail.kiz.ac.cn |
| 英文摘要 | AIM: To evaluate the anti-HIV activity and mechanism of action of wikstroelide M, a daphnane diterpene from Daphne acutiloba Rehder (Thymelaeaceae). METHOD: The anti-HIV activities of wikstroelide M against different HIV strains were evaluated by cytopathic effect assay and p24 quantification assay with ELISA. The inhibitory effect of wikstroelide M on HIV reverse transcription was analyzed by real-tithe PCR and ELISA. The effect of wikstroelide M on HIV-1 integrase nuclear translocation was observed with a cell-based imaging assay. The effect of wikstroelide M on LEDGF/p75-IN interaction was assayed by molecular docking. RESULTS: Wikstroelide M potently inhibited different HIV-1 strains, including HIV-1(IIIB), HIV-1(A17), and HIV-1(9495), induced a cytopathic effect, with EC50 values ranging from 3.81 to 15.65 ng.mL(-1). Wikstroelide M also had high inhibitory activities against HIV-2(ROD) and HIV-2(CBL-20)-induced cytopathic effects with EC50 values of 18.88 and 31.90 ng.mL(-1). The inhibitory activities of wikstroelide M (on) the three HIV-1 strains were further confirmed by p24 quantification assay, with EC50 values ranging from 15.16 to 35.57 ng.mL(-1). Wikstroelide M also potently inhibited HIV-1(IIIB) induced cytolysis in MT-4 cells, with an EC50 value of 9.60 ng.mL(-1). The mechanistic assay showed that wikstroelide M targeted HIV-1 reverse transcriptase and nuclear translocation of integrase through disrupting the interaction between integrase and LEDGF/p75. CONCLUSION: Wikstroelide M may be a potent HIV-1 and HIV-2 inhibitor, the mechanisms of action may include inhibition of reverse trascriptase activity and inhibition of integrase nuclear translocation through disrupting the interaction between integrase and LEDGF/p75. |
| 收录类别 | SCI |
| 资助信息 | This project was supported, in part, by grants from the National Natural Science Foundation of China (Nos. 81102483, 81001462), the 973 Program (No. 2009CB522306) and the Key Scientific and Techno- logical Program of China (Nos. 2009-ZX09501-029, 2012ZX10001- 006, 2012ZX10001-007, 2012ZX- 09103-101-022), and Yunnan (No. 2010GA001). |
| 语种 | 英语 |
| 公开日期 | 2014-06-03 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7844]  |
| 专题 | 昆明动物研究所_分子免疫药理学 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
| 作者单位 | 1.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Kunming Institute of Zoology, Chi- nese Academy of Sciences, Kunming 650223, China 2.Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China 3.School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China 4.School of Biomedical Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China 5.School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China |
| 推荐引用方式 GB/T 7714 | Zhang X,Huang SZ,Gu WG,et al. Wikstroelide M potently inhibits HIV replication by targeting reverse transcriptase and integrase nuclear translocation[J]. Chinese Journal of Natural Medicines,2014,12(3):186-193. |
| APA | Zhang X.,Huang SZ.,Gu WG.,Yang LM.,Chen H.,...&Zheng YT[*].(2014).Wikstroelide M potently inhibits HIV replication by targeting reverse transcriptase and integrase nuclear translocation.Chinese Journal of Natural Medicines,12(3),186-193. |
| MLA | Zhang X,et al."Wikstroelide M potently inhibits HIV replication by targeting reverse transcriptase and integrase nuclear translocation".Chinese Journal of Natural Medicines 12.3(2014):186-193. |
入库方式： OAI收割
来源：昆明动物研究所
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