Wapling Johanna, Srivastava Seema, Shehu-Xhilaga Miranda, Tachedjian Gilda
Molecular Interactions Group, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, 3004, Australia.
Drug Target Insights. 2007;2:159-82. Epub 2007 Jul 20.
The targets for licensed drugs used for the treatment of human immunodeficiency virus type 1 (HIV-1) are confined to the viral reverse transcriptase (RT), protease (PR), and the gp41 transmembrane protein (TM). While currently approved drugs are effective in controlling HIV-1 infections, new drug targets and agents are needed due to the eventual emergence of drug resistant strains and drug toxicity. Our increased understanding of the virus life-cycle and how the virus interacts with the host cell has unveiled novel mechanisms for blocking HIV-1 replication. This review focuses on inhibitors that target the late stages of virus replication including the synthesis and trafficking of the viral polyproteins, viral assembly, maturation and budding. Novel approaches to blocking the oligomerization of viral enzymes and the interactions between viral proteins and host cell factors, including their feasibility as drug targets, are discussed.
用于治疗1型人类免疫缺陷病毒(HIV-1)的已获许可药物的靶点局限于病毒逆转录酶(RT)、蛋白酶(PR)和gp41跨膜蛋白(TM)。虽然目前获批的药物在控制HIV-1感染方面有效,但由于最终会出现耐药菌株和药物毒性,仍需要新的药物靶点和药物。我们对病毒生命周期以及病毒与宿主细胞相互作用的深入了解揭示了阻断HIV-1复制的新机制。本综述重点关注靶向病毒复制后期的抑制剂,包括病毒多聚蛋白的合成和运输、病毒组装、成熟和出芽。还讨论了阻断病毒酶寡聚化以及病毒蛋白与宿主细胞因子之间相互作用的新方法,包括它们作为药物靶点的可行性。