Koup R A, Merluzzi V J, Hargrave K D, Adams J, Grozinger K, Eckner R J, Sullivan J L
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01605.
J Infect Dis. 1991 May;163(5):966-70. doi: 10.1093/infdis/163.5.966.
The dipyridodiazepinone human immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase (RT) inhibitor BI-RG-587 was tested for its ability to inhibit HIV-1 replication in both acutely and chronically infected cell lines. The ability of BI-RG-587 to inhibit steps in the virus replicative cycle other than reverse transcription was also assessed. BI-RG-587 was found to be a potent inhibitor of HIV-1 replication in acutely infected cells (50% inhibitory concentration [IC50] = 37.2 nM), and the sensitivity and kinetics of that inhibition was similar to the known RT inhibitor zidovudine (AZT). Even at 100x IC50, BI-RG-587 had no effect on gp120/CD4 interaction, syncytia formation, or envelope glycoprotein processing. In addition, no inhibition of viral replication or protein production was noted in a chronically infected cell line that produces viral products in an RT-independent manner. Finally, no inhibition of acute HIV-2 replication was noted, even with very high (2500x IC50 for HIV-1) concentrations of BI-RG-587. These results demonstrate that BI-RG-587 is a potent inhibitor of HIV-1 replication and that this inhibition occurs at the point of reverse transcription.
对二吡啶二氮杂卓酮类人类免疫缺陷病毒1型（HIV-1）特异性逆转录酶（RT）抑制剂BI-RG-587进行了测试，以评估其在急性和慢性感染细胞系中抑制HIV-1复制的能力。还评估了BI-RG-587抑制病毒复制周期中逆转录以外步骤的能力。结果发现，BI-RG-587是急性感染细胞中HIV-1复制的有效抑制剂（50%抑制浓度[IC50]=37.2 nM），这种抑制的敏感性和动力学与已知的RT抑制剂齐多夫定（AZT）相似。即使在100倍IC50浓度下，BI-RG-587对gp120/CD4相互作用、细胞融合或包膜糖蛋白加工也没有影响。此外，在以非RT依赖方式产生病毒产物的慢性感染细胞系中，未观察到对病毒复制或蛋白质产生的抑制作用。最后，即使使用非常高浓度（相对于HIV-1为2500倍IC50）的BI-RG-587，也未观察到对急性HIV-2复制的抑制作用。这些结果表明，BI-RG-587是HIV-1复制的有效抑制剂，且这种抑制作用发生在逆转录阶段。
