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Discovery of a novel HIV-1 integrase inhibitor from natural compounds through structure based virtual screening and cell imaging
- Source :
- FEBS Letters. (18):3461-3468
- Publisher :
- Federation of European Biochemical Societies. Published by Elsevier B.V.
-
Abstract
- The interaction between HIV-1 integrase and LEDGF/P75 has been validated as a target for anti-HIV drug development. Based on the crystal structure of integrase in complex with LEDGF/P75, a library containing 80 thousand natural compounds was filtered with virtual screening. 11 hits were selected for cell based assays. One compound, 3-(1,3-benzothiazol-2-yl)-8-{[bis(2-hydroxyethyl)amino]methyl}-7-hydroxy-2H-chromen-2-one (D719) inhibited integrase nuclear translocation in cell imaging. The binding mode of D719 was analyzed with molecular simulation. The anti-HIV activity of D719 was assayed by measuring the p24 antigen production in acute infection. The structure characteristics of D719 may provide valuable information for integrase inhibitor design.
- Subjects :
- Models, Molecular
Virtual screening
Stereochemistry
Cell
Active Transport, Cell Nucleus
Drug Evaluation, Preclinical
HIV Core Protein p24
Biophysics
Integrase inhibitor
Acute infection
HIV Integrase
Biochemistry
Coumarins
Structural Biology
Catalytic Domain
HIV-1 integrase
Genetics
medicine
Humans
Computer Simulation
Benzothiazoles
HIV Integrase Inhibitors
Molecular Biology
biology
Lens epithelium-derived growth factor (LEDGF/P75)
Cell Biology
Integrase
medicine.anatomical_structure
Drug development
HIV-1
Hiv 1 integrase
biology.protein
Structure based
HeLa Cells
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 00145793
- Issue :
- 18
- Database :
- OpenAIRE
- Journal :
- FEBS Letters
- Accession number :
- edsair.doi.dedup.....284de153b9cc37cb033450f3d5329c94
- Full Text :
- https://doi.org/10.1016/j.febslet.2014.08.004