title: Identification of an HIV-1 replication inhibitor which rescues host restriction factor APOBEC3G in Vif-APOBEC3G complex.
abstract: 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, IC50 = 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.
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Shaoyang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Clinical Laboratory, Guangdong NO. 2 Provincial People's Hospital, Guangzhou 510080, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Pan
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Liting
authors.initials: L
authors.lastname: Liang
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Qianwen
authors.initials: Q
authors.lastname: Li
authors.affiliation: Guangzhou Molcalx Information & Technology Ltd., 34 Longkou East Road, Unit No. 2002, Tianhe District, Guangzhou City 510630, China.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Haihua
authors.initials: H
authors.lastname: Luo
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: baichuan@mail.sysu.edu.cn.
authors.forename: Chuan
authors.initials: C
authors.lastname: Bai
mesh_terms: D000071480:APOBEC-3G Deaminase; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D044842:Cullin Proteins / Q000378:metabolism; D003564:Cytidine Deaminase / Q000737:chemistry* / Q000378:metabolism; D055808:Drug Discovery; D000075065:Elongin; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D062105:Molecular Docking Simulation; D014157:Transcription Factors / Q000378:metabolism; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; C496871:CUL5 protein, human; D044842:Cullin Proteins; C000616395:ELOC protein, human; C000616411:Eloc protein, mouse; D000075065:Elongin; D014157:Transcription Factors; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase
keywords: APOBEC3G; Elongin C; HIV-1; Vif; ZBMA-1