Targeting the Viral Polymerase of Diarrhea-Causing Viruses as a Strategy to Develop a Single Broad-Spectrum Antiviral Therapy

Viruses. 2019 Feb 20;11(2):173. doi: 10.3390/v11020173.

Abstract

Viral gastroenteritis is an important cause of morbidity and mortality worldwide, being particularly severe for children under the age of five. The most common viral agents of gastroenteritis are noroviruses, rotaviruses, sapoviruses, astroviruses and adenoviruses, however, no specific antiviral treatment exists today against any of these pathogens. We here discuss the feasibility of developing a broad-spectrum antiviral treatment against these diarrhea-causing viruses. This review focuses on the viral polymerase as an antiviral target, as this is the most conserved viral protein among the diverse viral families to which these viruses belong to. We describe the functional and structural similarities of the different viral polymerases, the antiviral effect of reported polymerase inhibitors and highlight common features that might be exploited in an attempt of designing such pan-polymerase inhibitor.

Keywords: DNA viruses; RNA viruses; antiviral; norovirus; rotavirus; viral polymerase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenovirus Infections, Human / drug therapy
  • Animals
  • Antiviral Agents / isolation & purification*
  • Antiviral Agents / therapeutic use
  • DNA Viruses / drug effects
  • DNA Viruses / enzymology
  • Diarrhea / drug therapy*
  • Diarrhea / virology*
  • Gastroenteritis / drug therapy*
  • Gastroenteritis / virology*
  • Humans
  • Norovirus / drug effects
  • Norovirus / enzymology
  • Nucleic Acid Synthesis Inhibitors / isolation & purification
  • Nucleic Acid Synthesis Inhibitors / therapeutic use
  • RNA Viruses / drug effects
  • RNA Viruses / enzymology
  • RNA-Dependent RNA Polymerase / metabolism*
  • Rotavirus / drug effects
  • Rotavirus / enzymology
  • Rotavirus Infections / drug therapy

Substances

  • Antiviral Agents
  • Nucleic Acid Synthesis Inhibitors
  • RNA-Dependent RNA Polymerase