 |
论文 |
|
|
 |
| 论文编号: |
|
| 论文题目: |
Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than Lamivudine in vitro. |
| 作者: |
Rui-Rui Wang, Qing-Hua Yang, Rong-Hua Luo, You-Mei Peng, Shao-Xing Dai, Xing-Jie Zhang, Huan Chen, Xue-Qing Cui, Ya-Juan Liu, Jing-Fei Huang, Jun-Biao Chang , Yong-Tang Zheng* |
| 联系作者: |
zhengyt@mail.kiz.ac.cn |
| 外单位作者单位: |
|
| 发表年度: |
2014 |
| 卷: |
9 |
| 期: |
8 |
| 页码: |
e105617 |
| 摘要: |
Azvudine is a novel nucleoside reverse transcriptase inhibitor with antiviral activity on human immunodeficiency virus, hepatitis B virus and hepatitis C virus. Here we reported the in vitro activity of azvudine against HIV-1 and HIV-2 when used alone or in combination with other antiretroviral drugs and its drug resistance features. Azvudine exerted highly potent inhibition on HIV-1 (EC50s ranging from 0.03 to 6.92 nM) and HIV-2 (EC50s ranging from 0.018 to 0.025 nM). It also showed synergism in combination with six approved anti-HIV drugs on both C8166 and PBMC. In combination assay, the concentrations of azvudine used were 1000 or 500 fold lower than other drugs. Azvudine also showed potent inhibition on NRTI-resistant strains (L74V and T69N). Although M184V caused 250 fold reduction in susceptibility, azvudine remained active at nanomolar range. In in vitro induced resistant assay, the frequency of M184I mutation increased with induction time which suggests M184I as the key mutation in azvudine treatment. As control, lamivudine treatment resulted in a higher frequency of M184I/V given the same induction time and higher occurrence of M184V was found. Molecular modeling analysis suggests that steric hindrance is more pronounced in mutant M184I than M184V due to the azido group of azvudine. The present data demonstrates the potential of azvudine as a complementary drug to current anti-HIV drugs. M184I should be the key mutation, however, azvudine still remains active on HIV-1LAI-M184V at nanomolar range. |
| 刊物名称: |
Plos One |
| 论文全文: |
点击查看 |
| 全文链接: |
点击下载 |
| Email:: |
|
| 学科: |
|
| 影响因子: |
3.234 (2014) |
| 第一作者所在部门: |
|
| 论文出处: |
|
| 论文类别: |
|
| 参与作者: |
|
|
|
