HIV-1 regulatory proteins: targets for novel drug development

Due to the development of HIV-1 resistance to current antiviral drugs and the known toxicity of many of these drugs, there is a clear need to identify and develop novel compounds for use in the treatment of HIV-1 infected patients. The HIV-1 regulatory proteins, Tat and Rev, are required for HIV-1 replication and therefore represent two important viral targets for drug development. Novel drugs that target these proteins would increase the number of available treatment strategies for HIV-1 infection. This could result in better combination therapies in which many different viral targets could be inhibited simultaneously, thereby decreasing the likelihood of selecting for drug-resistant viruses. This review outlines many of the ways that Tat and Rev can be targeted for drug development, describes recently reported lead compounds as inhibitors of these proteins and discusses strategies for implementing drug screens for identifying novel inhibitors.     

HIV-1 regulatory proteins: targets for novel drug development

Due to the development of HIV-1 resistance to current antiviral drugs and the known toxicity of many of these drugs, there is a clear need to identify and develop novel compounds for use in the treatment of HIV-1 infected patients. The HIV-1 regulatory proteins, Tat and Rev, are required for HIV-1 replication and therefore represent two important viral targets for drug development. Novel drugs that target these proteins would increase the number of available treatment strategies for HIV-1 infection. This could result in better combination therapies in which many different viral targets could be inhibited simultaneously, thereby decreasing the likelihood of selecting for drug-resistant viruses. This review outlines many of the ways that Tat and Rev can be targeted for drug development, describes recently reported lead compounds as inhibitors of these proteins and discusses strategies for implementing drug screens for identifying novel inhibitors.     

三个非核苷类逆转录酶抑制剂S-DABO类衍生物的体外抗HIV作用

本文对3个新S-DABO类衍合物 (RZK-4、RZK-5、RZK-6) 的体外抗HIV活性进行了研究。化合物RZK-4、RZK-5和RZK-6在200 µg·mL⁻¹的浓度下均能完全抑制HIV-1逆转录酶的活性。3个化合物对多种细胞均呈现出低毒性, 且均在较低浓度下具有抑制HIV-1病毒实验株、临床株和耐药株的作用, 治疗指数为3 704～38 462。其中, 化合物RZK-6对HIV-1耐药株HIV-1_IIIB A17具有非常显著的抑制作用。结果表明, 这3种S-DABO类衍生物有良好的体外抗HIV-1作用, 具有开发成为抗HIV-1药物的前景。