Identification of an HIV-1 replication inhibitor which rescues host restriction factor APOBEC3G in Vif-APOBEC3G complex

Antiviral Res. 2015 Oct:122:20-7. doi: 10.1016/j.antiviral.2015.07.009. Epub 2015 Aug 1.

Abstract

HIV-1 Vif protein is one of the most crucial accessory proteins for viral replication. It efficiently counteracts the important host restriction factor APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G, A3G) which is lethal to HIV-1 by causing G to A mutation of viral genome. Vif protein mediates degradation of APOBEC3G via the complicated protein-protein interactions of Vif, APOBEC3G, Elongin C/B and Cullin 5. The importance of Vif-APOBEC3G complex makes it a good potential target to develop new therapeutics of HIV-1. We identified a potent HIV-1 replication inhibitor (ZBMA-1, IC50 = 1.01 μM) that efficiently protected APOBEC3G protein by targeting Vif-APOBEC3G complex. The co-immunoprecipitation and docking studies indicated that compound ZBMA-1 affected the binding of Elongin C with Vif protein.

Keywords: APOBEC3G; Elongin C; HIV-1; Vif; ZBMA-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC-3G Deaminase
  • Animals
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / pharmacology*
  • Cullin Proteins / metabolism
  • Cytidine Deaminase / chemistry*
  • Cytidine Deaminase / metabolism
  • Drug Discovery
  • Elongin
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Immunoprecipitation
  • Mice
  • Molecular Docking Simulation
  • Transcription Factors / metabolism
  • vif Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • Anti-HIV Agents
  • CUL5 protein, human
  • Cullin Proteins
  • ELOC protein, human
  • Eloc protein, mouse
  • Elongin
  • Transcription Factors
  • vif Gene Products, Human Immunodeficiency Virus
  • vif protein, Human immunodeficiency virus 1
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human
  • Cytidine Deaminase