The many faces of the flavivirus NS1 protein offer a multitude of options for inhibitor design

Antiviral Res. 2016 Jun:130:7-18. doi: 10.1016/j.antiviral.2016.02.014. Epub 2016 Mar 2.

Abstract

The flavivirus non-structural protein, NS1, is an unusual viral gene product. Despite the recent unveiling of its atomic structure (Akey et al., 2014), and a growing list of host molecules with which it has been found associated, the primary function of NS1 remains elusive. It assumes many diverse roles including direct participation in the flaviviral replication complex and virion maturation. In its secreted form it is a hexameric lipoparticle that is involved in systemic immune and endothelial cell modulation. In this review we highlight recent advances in elucidating the molecular mechanisms underpinning NS1 function and present the current state of play and some future prospects for NS1 targeted antiviral strategies. This article forms part of a symposium on flavivirus drug discovery in Antiviral Research.

Keywords: Antiviral; Complement; Dengue; Flavivirus; Inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Membrane / metabolism
  • Drug Design*
  • Flavivirus / drug effects*
  • Flavivirus / genetics
  • Flavivirus / metabolism*
  • Gene Expression Regulation, Viral
  • Humans
  • Lipid Metabolism
  • Lipids / chemistry
  • Models, Molecular
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization
  • Protein Processing, Post-Translational
  • RNA Processing, Post-Transcriptional
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism*

Substances

  • Antiviral Agents
  • Lipids
  • NS1 protein, Flavivirus
  • Viral Nonstructural Proteins