1. Academic Validation
  2. Discovery of inhibitors to block interactions of HIV-1 integrase with human LEDGF/p75 via structure-based virtual screening and bioassays

Discovery of inhibitors to block interactions of HIV-1 integrase with human LEDGF/p75 via structure-based virtual screening and bioassays

  • J Med Chem. 2012 Nov 26;55(22):10108-17. doi: 10.1021/jm301226a.
Guoping Hu 1 Xi Li Xuan Zhang Yaozong Li Lei Ma Liu-Meng Yang Guixia Liu Weihua Li Jin Huang Xu Shen Lihong Hu Yong-Tang Zheng Yun Tang
Affiliations

Affiliation

  • 1 Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Abstract

This study aims to identify inhibitors that bind at the interface of HIV-1 integrase (IN) and human LEDGF/p75, which represents a novel target for anti-HIV therapy. To date, only a few such inhibitors have been reported. Here structure-based virtual screening was performed to search for the inhibitors from an in-house library of Natural Products and their derivatives. Among the 38 compounds selected by our strategy, 18 hits were discovered. The two most potent inhibitors showed IC(50) values at 0.32 and 0.26 μM, respectively. Three compounds were subsequently selected for anti-HIV assays, among which (E)-3-(2-chlorophenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one (NPD170) showed the highest Antiviral activity (EC(50) = 1.81 μM). The Antiviral mechanism of these compounds was further explored, and the results validated that the compounds interrupted the binding of transfected IN to endogenous LEDGF/p75. These findings could be helpful for anti-HIV drug discovery.

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