Norovirus drug candidates that inhibit viral capsid attachment to human histo-blood group antigens

Antiviral Res. 2016 Sep:133:14-22. doi: 10.1016/j.antiviral.2016.07.006. Epub 2016 Jul 13.

Abstract

Human noroviruses are the leading causative agents of epidemic and sporadic viral gastroenteritis and childhood diarrhoea worldwide. Human histo-blood group antigens (HBGA) serve as receptors for norovirus capsid protein attachment and play a critical role in infection. This makes HBGA-norovirus binding a promising target for drug development. Recently solved crystal structures of norovirus bound to HBGA have provided a structural basis for identification of potential anti-norovirus drugs and subsequently performed in silico and in vitro drug screens have identified compounds that block norovirus binding and may thereby serve as structural templates for design of therapeutic norovirus inhibitors. This review explores norovirus therapeutic options based on the strategy of blocking norovirus-HBGA binding.

Keywords: Antiviral therapy; Binding inhibitors; Human histo-blood group antigen; Norovirus; Norovirus capsid proteins.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Binding Sites
  • Blood Group Antigens / chemistry
  • Blood Group Antigens / metabolism*
  • Capsid Proteins / metabolism*
  • Computer Simulation
  • Drug Evaluation, Preclinical
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Norovirus / drug effects*
  • Norovirus / physiology*
  • Protein Binding / drug effects
  • Receptors, Virus / chemistry
  • Receptors, Virus / metabolism

Substances

  • Antiviral Agents
  • Blood Group Antigens
  • Capsid Proteins
  • Receptors, Virus