Vanpouille Christophe, Khandazhinskaya Anastasia, Karpenko Inna, Zicari Sonia, Barreto-de-Souza Victor, Frolova Svetlana, Margolis Leonid, Kochetkov Sergey
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation.
Antiviral Res. 2014 Sep;109:125-31. doi: 10.1016/j.antiviral.2014.06.019. Epub 2014 Jul 7.
Although more-recently developed antivirals target different molecules in the HIV-1 replication cycle, nucleoside reverse transcriptase inhibitors (NRTIs) remain central for HIV-1 therapy. Here, we test the anti-HIV activity of a phosphonate chimera of two well-known NRTIs, namely AZT and 3TC. We show that this newly synthesized compound suppressed HIV-1 infection in lymphoid tissue ex vivo more efficiently than did other phosphonates of NRTIs. Moreover, the new compound was not toxic for tissue cells, thus making the chimeric phosphonate strategy a valid approach for the development of anti HIV-1 compound heterodimers.
尽管最近开发的抗病毒药物针对HIV-1复制周期中的不同分子,但核苷类逆转录酶抑制剂(NRTIs)仍是HIV-1治疗的核心药物。在此,我们测试了两种著名NRTIs(即齐多夫定和拉米夫定)的膦酸嵌合体的抗HIV活性。我们发现,这种新合成的化合物在体外对淋巴组织中HIV-1感染的抑制作用比其他NRTIs膦酸酯更有效。此外,这种新化合物对组织细胞无毒,因此使嵌合膦酸酯策略成为开发抗HIV-1复合异二聚体的有效方法。