Sachs M K
Division of Infectious Disease, Jefferson Medical College, Philadelphia, Pa.
Arch Intern Med. 1992 Mar;152(3):485-501.
The intense research effort to develop molecules with the ability to inhibit the replication of human immunodeficiency virus type 1 was greatly facilitated by the elucidation of the viral life cycle. This information engendered the production of novel antiretroviral agents that inhibit human immunodeficiency virus type 1 at different points in its replicative cycle. The nucleoside analogue 3'-azido-2',3'-dideoxythymidine (azidothymidine) inhibits reverse transcriptase, and it was the first compound tested in patients with the acquired immunodeficiency syndrome. Considerable knowledge of the activity and toxicity of this class of drugs has accumulated. Less well-characterized compounds inhibit human immunodeficiency virus type 1 binding and absorption to target cells, prevent the expression of viral genetic material critical for the construction of new infectious viral progeny, and inhibit the posttranslational modification of viral polypeptides. In additional, biologic response, modifiers act to restore immune function by a number of diverse mechanisms. The ultimate goal is the discovery of compounds capable of inducing a complete and permanent remission of infection.
对人类免疫缺陷病毒1型复制具有抑制能力的分子的深入研究,因病毒生命周期的阐明而得到极大推动。这一信息催生了新型抗逆转录病毒药物的研发,这些药物可在人类免疫缺陷病毒1型复制周期的不同阶段发挥抑制作用。核苷类似物3'-叠氮-2',3'-双脱氧胸腺嘧啶核苷(叠氮胸苷)可抑制逆转录酶,它是首个在获得性免疫缺陷综合征患者身上进行试验的化合物。关于这类药物的活性和毒性,人们已经积累了相当多的知识。还有一些特性了解较少的化合物,它们可抑制人类免疫缺陷病毒1型与靶细胞的结合及吸附,阻止对构建新的感染性病毒后代至关重要的病毒遗传物质的表达,并抑制病毒多肽的翻译后修饰。此外,生物反应调节剂可通过多种不同机制来恢复免疫功能。最终目标是发现能够诱导感染完全且永久缓解的化合物。