Polyether antibiotics K-41A and K-41Am inhibit HIV-1 replication via suppressing the activities of HIV-1 reverse transcriptase and integrase
Polyether antibiotics K-41A and K-41Am inhibit HIV-1 replication via suppressing the activities of HIV-1 reverse transcriptase and integrase
复制标题
聚醚抗生素 K-41A 和 K-41Am 通过抑制 HIV-1 逆转录酶和整合酶的活性来抑制 HIV-1 复制
DOI：
10.5114/aoms.2020.98038
复制
发表时间：
2020
影响因子：
3.8
通讯作者：
Hao Liang
中科院分区：
文献类型：
--
作者：
Xin Liu;Jiemei Chu;Chun Gui;Weibo Liao;Fengxiang Qin;Xi Hu;Bingyu Liang;Junjun Jiang;Jiegang Huang;Chuanyi Ning;Jiang Chen;Jianhua Ju;Jingzhen Lai;Jie Liu;Bo Zhou;Li Ye;Hao Liang
Introduction: K-41A is a known compound with antibacterial activity against gram-positive bacteria and coccidia. In our screening of anti-HIV compounds, we found polyether antibiotic K-41A and its analogue K-41Am isolated from a marine-derived Streptomyces sp. SCSIO 01680 exhibited anti-HIV activity. Material and methods: In this study, we characterised the anti-HIV activity of K-41A and K-41Am as well as the mechanism(s) involved. The dose-dependent inhibitory effects of K-41A and K-41Am on HIV-1 replication were observed in the TZM-bl-HIV-1IIIB system, MT-2-HIV-1IIIB system, and peripheral blood mononuclear cells (PBMCs)-HIV-1BaL system. The 50% inhibitory concentrations (IC50) of K-41A on HIV-1 replication in three systems were 0.75 μM, 0.09 μM, and 0.13 μM, respectively, and the selective indexes (SIs) were 5.81, 49.44, and 598.00, respectively. The IC50 of K-41Am in three systems were 5.57 μM, 0.24 μM, and 1.15 μM, respectively, and the SIs were > 1.04, 80.71, and > 5.03, respectively. Results: Mechanism research demonstrates that two compounds inhibited the activities of HIV-1 reverse transcriptase (RT) and integrase (IN) in a dose-dependent manner. Molecular docking shows that the docking scores were relatively high between the compound and HIV-1 RT or IN. Conclusions: K-41A and K-41Am possess anti-HIV-1 activity via a multi-target inhibition mechanism, which provides a novel molecular pattern for anti-HIV drug design and structural modification to improve the anti-HIV activity.
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DOI：
10.7164/antibiotics.55.832
发表时间：
2002-09
期刊：
The Journal of antibiotics
影响因子：
--
作者：
K. Otoguro;Aki Ishiyama;H. Ui;Miyuki Kobayashi;Chizu Manabe;G. Yan;Yōko Takahashi;Haruo Tanaka;H. Yamada;S. Ōmura
通讯作者：
K. Otoguro;Aki Ishiyama;H. Ui;Miyuki Kobayashi;Chizu Manabe;G. Yan;Yōko Takahashi;Haruo Tanaka;H. Yamada;S. Ōmura
DOI：
10.7164/antibiotics.50.631
发表时间：
1997-07
期刊：
The Journal of antibiotics
影响因子：
--
作者：
M. Hoshi;K. Shimotohno;T. Endō;K. Furihata;H. Seto
通讯作者：
M. Hoshi;K. Shimotohno;T. Endō;K. Furihata;H. Seto
影响因子：
6.7
作者：
Cátia Teixeira;J. R. Gomes;P. Gomes;F. Maurel;F. Barbault
通讯作者：
Cátia Teixeira;J. R. Gomes;P. Gomes;F. Maurel;F. Barbault
影响因子：
158.5
作者：
Gulick, RM;Mellors, JW;Chodakewitz, JA
通讯作者：
Chodakewitz, JA
影响因子：
56.9
作者：
BARRESINOUSSI, F;CHERMANN, JC;MONTAGNIER, L
通讯作者：
MONTAGNIER, L