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Identification of an HIV-1 replication inhibitor which rescues host restriction factor APOBEC3G in Vif–APOBEC3G complex

Shaoyang Zhang,Limei Zhong,Bing Chen,Ting Pan,Xue Zhang,Liting Liang,Qianwen Li,Ziying Zhang,Hui Chen,Jie Zhou,Haihua Luo,Hui Zhang,Chuan Bai

HIV-1 Vif protein is one of the most crucial accessory proteins for viral replication. It efficiently counteracts the important host restriction factor APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G, A3G) which is lethal to HIV-1 by causing G to A mutation of viral genome. Vif protein mediates degradation of APOBEC3G via the complicated protein–protein interactions of Vif, APOBEC3G, Elongin C/B and Cullin 5. The importance of Vif–APOBEC3G complex makes it a good potential target to develop new therapeutics of HIV-1. We identified a potent HIV-1 replication inhibitor (ZBMA-1, IC 50   =   1.01   μM) that efficiently protected APOBEC3G protein by targeting Vif–APOBEC3G complex. The co-immunoprecipitation and docking studies indicated that compound ZBMA-1 affected the binding of Elongin C with Vif protein.