Identification of small molecule compounds targeting the interaction of HIV-1 Vif and human APOBEC3G by virtual screening and biological evaluation

  • Sci Rep. 2018 May 23;8(1):8067. doi: 10.1038/s41598-018-26318-3.
Ling Ma  1 ,  Zhixin Zhang  1 ,  Zhenlong Liu  2 ,  Qinghua Pan  2 ,  Jing Wang  1 ,  Xiaoyu Li  3 ,  Fei Guo  4 ,  Chen Liang  2 ,  Laixing Hu  1 ,  Jinming Zhou  5 ,  Shan Cen  6
Affiliations
  • 1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 2. Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, QC, Canada.
  • 3. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. [email protected].
  • 4. Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 5. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. [email protected].
  • 6. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. [email protected].
PMID: 29795228 DOI: 10.1038/s41598-018-26318-3
Abstract

Human APOBEC3G (hA3G) is a restriction factor that inhibits human immunodeficiency 1 virus (HIV-1) replication. The virally encoded protein Vif binds to hA3G and induces its degradation, thereby counteracting the Antiviral activity of hA3G. Vif-mediated hA3G degradation clearly represents a potential target for anti-HIV drug development. Herein, we have performed virtual screening to discover small molecule inhibitors that target the binding interface of the Vif/hA3G complex. Subsequent biochemical studies have led to the identification of a small molecule inhibitor, IMB-301 that binds to hA3G, interrupts the hA3G-Vif interaction and inhibits Vif-mediated degradation of hA3G. As a result, IMB-301 strongly inhibits HIV-1 replication in a hA3G-dependent manner. Our study further demonstrates the feasibility of inhibiting HIV replication by abrogating the Vif-hA3G interaction with small molecules.

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