Mitsuya H, Yarchoan R, Broder S
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Science. 1990 Sep 28;249(4976):1533-44. doi: 10.1126/science.1699273.
The development of antiretroviral therapy against acquired immunodeficiency syndrome (AIDS) has been an intense research effort since the discovery of the causative agent, human immunodeficiency virus (HIV). A large array of drugs and biologic substances can inhibit HIV replication in vitro. Nucleoside analogs--particularly those belonging to the dideoxynucleoside family--can inhibit reverse transcriptase after anabolic phosphorylation. 3'-Azido-2',3'-dideoxythymidine (AZT) was the first such drug tested in individuals with AIDS, and considerable knowledge of structure-activity relations has emerged for this class of drugs. However, virtually every step in the replication of HIV could serve as a target for a new therapeutic intervention. In the future, non-nucleoside-type drugs will likely become more important in the experimental therapy of AIDS, and antiretroviral therapy will exert major effects against the morbidity and mortality caused by HIV.
自从发现获得性免疫缺陷综合征（艾滋病）的病原体——人类免疫缺陷病毒（HIV）以来，抗逆转录病毒疗法的研发一直是一项高强度的研究工作。大量药物和生物物质在体外可抑制HIV复制。核苷类似物——特别是那些属于双脱氧核苷家族的类似物——在合成代谢磷酸化后可抑制逆转录酶。3'-叠氮-2',3'-双脱氧胸苷（AZT）是首个在艾滋病患者中进行测试的此类药物，对于这类药物，已经积累了相当多的构效关系知识。然而，HIV复制过程中的几乎每一步都可能成为新的治疗干预靶点。未来，非核苷类药物在艾滋病实验治疗中可能会变得更加重要，抗逆转录病毒疗法将对HIV所致的发病率和死亡率产生重大影响。
