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

被引：24

作者：

Zhang, Shaoyang ^{[1
]}

Zhong, Limei ^{[2
]}

Chen, Bing ^{[1
]}

Pan, Ting ^{[1
]}

Zhang, Xue ^{[1
]}

Liang, Liting ^{[1
]}

Li, Qianwen ^{[1
]}

Zhang, Ziying ^{[4
]}

Chen, Hui ^{[1
]}

Zhou, Jie ^{[1
]}

Luo, Haihua ^{[1
]}

Zhang, Hui ^{[1
,3
]}

Bai, Chuan ^{[1
,3
]}

机构：

[1] Sun Yat Sen Univ, Zhongshan Sch Med, Inst Human Virol, Guangzhou 510080, Guangdong, Peoples R China

[2] Guangdong 2 Prov Peoples Hosp, Clin Lab, Guangzhou 510080, Guangdong, Peoples R China

[3] Sun Yat Sen Univ, Zhongshan Sch Med, Minist Educ, Key Lab Trop Dis Control, Guangzhou 510080, Guangdong, Peoples R China

[4] Guangzhou Molcalx Informat & Technol Ltd, Guangzhou, Guangdong, Peoples R China

来源：

ANTIVIRAL RESEARCH | 2015年 / 122卷

基金：

中国国家自然科学基金; 高等学校博士学科点专项科研基金;

关键词：

HIV-1; Vif; APOBEC3G; Elongin C; ZBMA-1; ANTIRETROVIRAL DRUG-RESISTANCE; IMMUNODEFICIENCY-VIRUS TYPE-1; SMALL-MOLECULE INHIBITION; E3 UBIQUITIN LIGASE; VIF PROTEIN; CYTIDINE DEAMINASE; ANTIVIRAL ACTIVITY; ENZYME APOBEC3G; UNITED-STATES; SOCS-BOX;

D O I：

10.1016/j.antiviral.2015.07.009

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 mu M) 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. (C) 2015 Elsevier B.V. All rights reserved.

引用

页码：20 / 27

页数：8

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