Design and synthesis of anti-HIV agents that inhibit the Vif-mediated proteasome degradation of APOBEC3G

APOBEC3G是一种阻断HIV-1复制的人类抗病毒蛋白。然而，A3G的抗病毒活性被降解APOBEC3G的HIV-1蛋白Vif所克服。我们设计并合成了人造化合物MF1、MF2和MF3来检测其抑菌活性。我们发现MF2和MF1（通过在MF2中加入DTT产生）使APOBEC3G的表达增加到远高于没有Vif时的水平，而不影响Vif的表达水平。此外，MF2、MF3和MF1（通过在MF2或MF3中添加DTT产生）显著抑制了野生型HIV-1的MAGI细胞感染。这些发现可能有助于开发一种新的抗hiv -1药物。

APOBEC3G is a human antiviral protein that blocks HIV-1 replication. However, the antiviral activity of A3G is overcome by the HIV-1 protein Vif that degrades APOBEC3G. We designed and synthesized artificial compounds MF1, MF2, and MF3 to examine the Vif-inhibitory activity. We found that MF2 and MF1(generated by adding DTT to MF2) increase the expression of APOBEC3G to a level much higher than that observed in the absence of Vif, without affecting the level of Vif expression. Furthermore, MF2, MF3, and MF1(generated by adding DTT to MF2 or MF3) significantly inhibited the MAGI cell infectivity of wild-type HIV-1. These findings may contribute to the development of a novel anti-HIV-1 drug.