Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking

doi:10.1007/s00894-012-1494-0

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第三研究室

	Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking
	Hu, Guoping 2; Li, Xi 2; Sun, Xianqiang 2; Lu, Weiqiang 2; Liu, Guixia 2; Huang, Jin 2; Shen, Xu1 ; Tang, Yun 2
刊名	JOURNAL OF MOLECULAR MODELING
	2012-12
卷号	18 期号:12 页码:4995-5003
关键词	Drug repositioning HIV-1 Integrase Human LEDGF/p75 protein Molecular docking Protein-protein interaction
ISSN号	1610-2940
DOI	10.1007/s00894-012-1494-0
文献子类	Article
英文摘要	Integration of viral-DNA into host chromosome mediated by the viral protein HIV-1 integrase (IN) is an essential step in the HIV-1 life cycle. In this process, human protein Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-factor for integration. LEDGF/p75-HIV-1 IN interaction represents an attractive target for anti-HIV therapy. In this study, approved drugs were investigated for the finding of potential inhibitors on this target. Via molecular docking against the LEDGF/p75-binding pocket of HIV-1 IN, 26 old drugs were selected from the DrugBank and purchased for bioassays. Among them, eight, namely Atorvastatin, Bumetanide, Candesartan, Carbidopa, Diclofenac, Diflunisal, Eprosartan, and Sulindac, were identified as potential inhibitors of LEDGF/p75- HIV-1 IN interaction, whose IC50 values ranged from 6.5 mu M to 36.8 mu M. In addition, Atorvastatin was previously reported to block HIV-1 replication and may have an important implication for the treatment of AIDS. Our results suggested a mechanism of action for the anti-HIV effects of Atorvastatin. This work provides a new example of inhibitors targeting protein-protein interaction and confirmed that old drugs were valuable sources for antiviral drug discovery.
资助项目	Program for New Century Excellent Talents in University[NCET-08-0774] ; Innovation Program of Shanghai Municipal Education Commission[10ZZ41] ; National Natural Science Foundation of China[90813005] ; National Natural Science Foundation of China[10979072] ; Specialized Research Fund for the Doctoral Program of Higher Education of China[20090074120012] ; 111 Project[B07023] ; Shanghai Committee of Science and Technology[11DZ2260600]
WOS关键词	PROTEIN-PROTEIN INTERACTIONS ; CELLULAR COFACTORS ; REPLICATION ; INSIGHTS ; DOMAIN
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Chemistry ; Computer Science
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000311400100004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277867]
专题	药理学第三研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Huang, Jin
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China;
推荐引用方式 GB/T 7714	Hu, Guoping,Li, Xi,Sun, Xianqiang,et al. Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking[J]. JOURNAL OF MOLECULAR MODELING,2012,18(12):4995-5003.
APA	Hu, Guoping.,Li, Xi.,Sun, Xianqiang.,Lu, Weiqiang.,Liu, Guixia.,...&Tang, Yun.(2012).Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking.JOURNAL OF MOLECULAR MODELING,18(12),4995-5003.
MLA	Hu, Guoping,et al."Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking".JOURNAL OF MOLECULAR MODELING 18.12(2012):4995-5003.