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

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

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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-122156
    99.08%, HIV-1 Inhibitor
    HIV