Studies of binding interactions between Dufulin and southern rice black-streaked dwarf virus P9-1

Bioorg Med Chem. 2015 Jul 1;23(13):3629-37. doi: 10.1016/j.bmc.2015.04.008. Epub 2015 Apr 10.

Abstract

Southern rice black-streaked dwarf virus (SRBSDV) is an important rice virus that can cause considerable crop losses. During infection, SRBSDV P9-1 accumulates viroplasms in SRBSDV-infected plant and insect cells, which may facilitate the formation of SRBSDV particles. Our field trial results showed that Dufulin inhibited infection activity in SRBSDV-infected rice. However it is not clear how Dufulin inhibits the infection activity. Therefore we studied the interactions between Dufulin and SRBSDV using P9-1 as a potential target, and found that Dufulin inhibited SRBSDV P9-1 gene expression and had a micromole affinity for the arginine 175 residue. Substituting arginine with glycine resulted in a mutant that was significantly less sensitive to Dufulin. Based on these results, we speculate that Dufulin inhibits the virulence of SRBSDV by binding with arginine 175 in the internal pore of P9-1 octameric protein.

Keywords: Arginine 175; Dufulin; P9-1 octamers; SRBSDV; Viroplasm formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Benzothiazoles / chemistry
  • Benzothiazoles / pharmacology*
  • Binding Sites
  • Cloning, Molecular
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Genes, Viral*
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Oryza / virology*
  • Plant Diseases / therapy
  • Protein Binding
  • Protein Multimerization
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Reoviridae / drug effects*
  • Reoviridae / genetics
  • Reoviridae / metabolism
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism
  • Virion / drug effects
  • Virion / growth & development
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Benzothiazoles
  • Recombinant Proteins
  • Viral Nonstructural Proteins
  • dufulin