Department of Microbiology and Immunology, McGill University, Lyman Duff Medical Building (D6), 3775 University St., Montreal, QC, H3A 2B4, Canada.
Viruses. 2010 Apr;2(4):900-926. doi: 10.3390/v2040900. Epub 2010 Mar 30.
Since the human immunodeficiency virus (HIV) was discovered as the etiological agent of acquired immunodeficiency syndrome (AIDS), it has encouraged much research into antiviral compounds. The reverse transcriptase (RT) of HIV has been a main target for antiviral drugs. However, all drugs developed so far inhibit the polymerase function of the enzyme, while none of the approved antiviral agents inhibit specifically the necessary ribonuclease H (RNase H) function of RT. This review provides a background on structure-function relationships of HIV-1 RNase H, as well as an outline of current attempts to develop novel, potent chemotherapeutics against a difficult drug target.
自人类免疫缺陷病毒 (HIV) 被发现是获得性免疫缺陷综合征 (AIDS) 的病因以来,它极大地促进了抗病毒化合物的研究。HIV 的逆转录酶 (RT) 一直是抗病毒药物的主要靶点。然而,迄今为止开发的所有药物都抑制了酶的聚合酶功能,而没有一种批准的抗病毒药物能够特异性抑制 RT 必需的核糖核酸酶 H (RNase H) 功能。本综述提供了 HIV-1 RNase H 的结构-功能关系的背景,以及目前开发针对这一困难药物靶点的新型有效化学疗法的概述。