Characterization of Antiviral Activity of Benzamide Derivative AH0109 against HIV-1 Infection

被引:17
作者
Chen, Liyu [1 ,2 ]
Ao, Zhujun [1 ]
Jayappa, Kallesh Danappa [1 ]
Kobinger, Gary [3 ]
Liu, ShuiPing [2 ]
Wu, Guojun [2 ]
Wainberg, Mark A. [4 ]
Yao, Xiaojian [1 ]
机构
[1] Univ Manitoba, Dept Med Microbiol, Fac Med, Lab Mol Human Retrovirol, Winnipeg, MB, Canada
[2] Cent S Univ, Sch Basic Med Sci, Dept Microbiol, Changsha, Hunan, Peoples R China
[3] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada
[4] McGill Univ, Jewish Gen Hosp, AIDS Ctr, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada
关键词
REVERSE-TRANSCRIPTASE; INTEGRASE; VIRUS; NUCLEAR; RESISTANCE; MUTATIONS; IDENTIFICATION; INHIBITORS; ETRAVIRINE; MECHANISM;
D O I
10.1128/AAC.00100-13
中图分类号
Q93 [微生物学];
学科分类号
071005 [微生物学];
摘要
In the absence of an effective vaccine against HIV-1 infection, anti-HIV-1 strategies play a major role in disease control. However, the rapid emergence of drug resistance against all currently used anti-HIV-1 molecules necessitates the development of new antiviral molecules and/or strategies against HIV-1 infection. In this study, we have identified a benzamide derivative named AH0109 that exhibits potent anti-HIV-1 activity at an 50% effective concentration of 0.7 mu M in HIV-1-susceptible CD4(+) C8166 T cells. Mechanistic analysis revealed that AH0109 significantly inhibits both HIV-1 reverse transcription and viral cDNA nuclear import. Furthermore, our infection experiments indicated that AH0109 is capable of disrupting the replication of HIV-1 strains that are resistant to the routinely used anti-HIV-1 drugs zidovudine, lamivudine, nevirapine, and raltegravir. Together, these findings provide evidence for a newly identified antiviral molecule that can potentially be developed as an anti-HIV-1 agent.
引用
收藏
页码:3547 / 3554
页数:8
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