Treatment with a Nucleoside Polymerase Inhibitor Reduces Shedding of Murine Norovirus in Stool to Undetectable Levels without Emergence of Drug-Resistant Variants

Antimicrob Agents Chemother. 2015 Dec 28;60(3):1907-11. doi: 10.1128/AAC.02198-15.

Abstract

Prolonged norovirus shedding may occur in certain patients, such as organ transplant recipients. We established a mouse model for persistent norovirus infection (using the mouse norovirus MNV.CR6 strain). The nucleoside viral polymerase inhibitor 2'-C-methylcytidine (2CMC), but not favipiravir (T-705), reduced viral shedding to undetectable levels. Viral rebound was observed after stopping treatment, which was again effectively controlled by treatment with 2CMC. No drug-resistant variants emerged.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / therapeutic use
  • Animals
  • Caliciviridae Infections / drug therapy*
  • Caliciviridae Infections / virology
  • Cytidine / analogs & derivatives*
  • Cytidine / therapeutic use
  • Disease Models, Animal
  • Feces / virology
  • Gastroenteritis / drug therapy*
  • Gastroenteritis / virology
  • Mice
  • Mice, Knockout
  • Norovirus / drug effects*
  • Norovirus / growth & development
  • Pyrazines / therapeutic use
  • Receptors, Interferon / genetics
  • Transplant Recipients
  • Virus Shedding / drug effects*

Substances

  • Amides
  • Pyrazines
  • Receptors, Interferon
  • 2'-C-methylcytidine
  • Cytidine
  • favipiravir