Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, PR China.
Curr Med Chem. 2010;17(6):495-503. doi: 10.2174/092986710790416335.
Although recent progress in highly active antiretroviral therapy (HAART) has provided an effective way to treat AIDS patients, the emergence of drug-resistant HIV-1 strains and drug toxicity during long-term treatment of HIV-infected patients necessitate the search for new targets that can be used to develop novel antiviral agents. One such target is the nuclear import process of the HIV pre-integration complex (PIC). The ability of HIV-1 using host cell nuclear import machinery to translocate the viral PIC into the cell nucleus is the critical determinant in the replication of the virus in non-dividing cells, such as macrophages. Compounds inhibiting HIV-1 nuclear import may be attractive candidates for novel anti-HIV development. In this review, we will describe the mechanisms of HIV-1 PIC translocation into the nucleus and the structure-function of the viral and cellular factors involved in this process, as well as several classes of novel anti-HIV compounds which target the nuclear import of HIV-1 PIC and effectively block viral replication.
虽然高效抗逆转录病毒疗法（HAART）的最新进展为治疗艾滋病患者提供了一种有效方法，但 HIV-1 耐药株的出现以及 HIV 感染者长期治疗过程中的药物毒性，需要寻找新的靶点，以开发新的抗病毒药物。其中一个靶点是 HIV 前整合复合物（PIC）的核输入过程。HIV-1 利用宿主细胞核输入机制将病毒 PIC 转运到细胞核内，这是病毒在非分裂细胞（如巨噬细胞）中复制的关键决定因素。抑制 HIV-1 核输入的化合物可能是新型抗 HIV 药物开发的有吸引力的候选药物。在这篇综述中，我们将描述 HIV-1 PIC 进入细胞核的机制，以及参与这一过程的病毒和细胞因子的结构和功能，以及几类针对 HIV-1 PIC 核输入的新型抗 HIV 化合物，这些化合物能有效阻断病毒复制。
