Inhibitors of HIV-1 Integrase-Human LEDGF/p75 Interaction Identified from Natural Products via Virtual Screening
Inhibitors of HIV-1 Integrase-Human LEDGF/p75 Interaction Identified from Natural Products via Virtual Screening作者机构：Shanghai Key Laboratory of New Drug Design School of Pharmacy East China University of Science and Technology Shanghai 20023 7 China State Key Laboratory of Drug Research Shanghai Institute ofMateria Medica Chinese Academy of Sciences Shanghai 201203 China
出 版 物：《Chinese Journal of Chemistry》 (中国化学（英文版）)
年 卷 期：2012年第30卷第12期
页 面：2752-2758页
核心收录：
学科分类：071011[理学-生物物理学] 0710[理学-生物学] 07[理学] 0828[工学-农业工程] 08[工学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种]
基 金：supported by the Program for New Century Excellent Talents in University (No. NCET-08-0774) the Innovation Program of Shanghai Municipal Education Commission (No. 10ZZ41) the National Natural Science Foundation of China (No. 21072059) and the Shanghai Committee of Science and Technology (No. 11DZ2260600). We thank the National Compound Resource Center for providing compounds. The cDNA coding for HIV IN CCD (residues 50-212) including the F185K solubilizing-mutation was a gift from Prof. Robert Craigie (National Institutes of Health Bethesda MD). The full-length plasmid pCPNat p75 was kindly provided by Prof. Zeger De- byser (Katholieke Universiteit Leuven Belgium)
主 题：natural products virtual screening protein-protein interaction HIV-1 integrase human LEDGF/p75protein
摘 要：HIV-1 integrase （IN）-mediated integration of viral DNA into the host chromosome is an essential step in the virus life cycle. Human lens epithelium-derived growth factor （LEDGF/p75） has been found to function as a cellu- lar cofactor in this process. The LEDGF/p75-1N interaction hence represents an attractive target for anti-HIV ther- apy. In this study, natural products were virtually screened against the LEDGF/p75 binding pocket of HIV-1 IN. 24 compounds were selected and obtained from the National Compound Resource Center of China. AlphaScreen as- says characterized 8 of these 24 natural products as potent LEDGF/p75-IN interaction inhibitors. The active com- pounds whose ICs0 values ranged from 0.56 to 14.55 ~mol/L could be used as lead compounds for further investi- gation. This work confirmed that natural products are valuable resources for antiviral drug discovery.
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