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Inhibitors of HIV‐1 Integrase‐Human LEDGF/p75 Interaction Identified from Natural Products via Virtual Screening
Author(s) -
Hu Guoping,
Li Xi,
Li Yaozong,
Sun Xianqiang,
Liu Guixia,
Li Weihua,
Huang Jin,
Shen Xu,
Tang Yun
Publication year - 2012
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201200897
Subject(s) - integrase , chemistry , virtual screening , function (biology) , viral life cycle , integrase inhibitor , drug discovery , human immunodeficiency virus (hiv) , natural product , computational biology , biochemistry , dna , microbiology and biotechnology , virology , gene , viral load , antiretroviral therapy , biology , rna
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 cellular cofactor in this process. The LEDGF/p75‐IN interaction hence represents an attractive target for anti‐HIV therapy. 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 assays characterized 8 of these 24 natural products as potent LEDGF/p75‐IN interaction inhibitors. The active compounds whose IC 50 values ranged from 0.56 to 14.55 µmol/L could be used as lead compounds for further investigation. This work confirmed that natural products are valuable resources for antiviral drug discovery.