INHIBITION OF HIV-1 REPLICATION BY C2 SYMMETRIC HIV PROTEASE INHIBITORS

HIV蛋白酶代表了一个重要的病毒特异性靶点， 艾滋病的治疗。这样的方法是一种抑制 在慢性HIV感染者中产生成熟的感染性病毒体 细胞 最近，已经研究了许多抗逆转录病毒肽类似物。 基于HIV-1的生理学和结构知识合成 蛋白酶 一类这样的蛋白酶抑制剂是C2对称蛋白酶 抑制剂. 当前HIV感染治疗方法的合理扩展 将是使用多种抗病毒剂的组合， 不同的抗逆转录病毒机制。 因此，我们探讨了 对称HIV蛋白酶抑制剂对多种HIV有活性 菌株，并与双脱氧核苷如AZT或ddl协同作用， 体外 我们也问过这样的抑制剂是否会引起不可逆的 HIV蛋白酶的变化 在本报告中，我们描述了C2 这项研究中测试的对称HIV蛋白酶抑制剂具有有效的 对多种HIV分离株具有抗病毒活性，包括 单核细胞嗜性菌株和主要HIV-1分离株。 我们还证明 并讨论了C2对称HIV蛋白酶的组合 抑制剂和AZT或ddI，双脱氧核苷类似物， 在临床领域。

The HIV protease represents a crucial virus-specific target for new therapies of AIDS. Such an approach is one way of inhibiting the production of mature, infectious virions in chronically HIV-infected cells. Recently, a number of antiretroviral peptide analogs have been synthesized based on the knowledge of physiology and structure of HIV-1 protease. One class of such protease inhibitors is C2 symmetric protease inhibitor. Logical extension of current approaches for therapy of HIV infection would be the use of combinations of multiple antiviral agents which have different antiretroviral mechanism(s). Thus, we have explored whether symmetric HIV protease inhibitors are active against a variety of HIV strains and synergize with dideoxynucleosides such as AZT or ddl in vitro. We have also asked whether such inhibitors cause irreversible changes to HIV protease. In the present report, we describe that C2 symmetric HIV protease inhibitors tested in this study had a potent antiviral activity against a wide range of HIV isolates including monocytotropic strains and primary HIV-1 isolates. We also demonstrate and discuss the effects of combinations of C2 symmetric HIV protease inhibitors and AZT or ddI, dideoxynucleoside analogues which are already in a clinical domain.