2. Academic Validation
  3. Discovery of a novel HIV-1 integrase inhibitor from natural compounds through structure based virtual screening and cell imaging

Discovery of a novel HIV-1 integrase inhibitor from natural compounds through structure based virtual screening and cell imaging

  • FEBS Lett. 2014 Sep 17;588(18):3461-8. doi: 10.1016/j.febslet.2014.08.004.
Wan-Gang Gu 1,  Xuan Zhang 2,  Denis Tsz-Ming Ip 3,  Liu-Meng Yang 2,  Yong-Tang Zheng 2,  David Chi-Cheong Wan 4
Affiliations

Affiliations

  • 1 School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; Department of Immunology, Zunyi Medical University, Zunyi, China.
  • 2 Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
  • 3 School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
  • 4 School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. Electronic address: [email protected].
PMID: 25128456 DOI: 10.1016/j.febslet.2014.08.004
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.

Keywords

HIV-1 integrase; Lens epithelium-derived growth factor (LEDGF/P75); Virtual screening.

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