文献类型： 外文期刊

作者： Zhang Xuan ¹ ; Huang Sheng-Zhuo ² ; Gu Wan-Gang ⁵ ; Yang Liu-Meng ¹ ; Chen Huan ¹ ; Zheng Chang-Bo; Zhao You-Xing ² ;

作者机构： 1.Chinese Acad Sci, Kunming Inst Zool, KIZ CUHK Joint Lab Bioresources & Mol Res Common, Key Lab Anim Models & Human Dis Mech,Chinese Acad, Kunming 650223, Peoples R China

2.Chinese Acad Trop Agr Sci, Inst Trop Biosci & Biotechnol, Haikou 571101, Peoples R China

3.Kunming Med Univ, Sch Pharmaceut Sci, Kunming 650500, Peoples R China

4.Kunming Med Univ, Yunnan Key Lab Pharmacol Nat Prod, Kunming 650500, Peoples R China

5.Chi

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

期刊名称：CHINESE JOURNAL OF NATURAL MEDICINES （ 影响因子：3.0； 五年影响因子：2.869 ）

ISSN： 2095-6975

年卷期： 2014 年 12 卷 3 期

页码：

收录情况： SCI

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.