Polyanionic carbosilane dendrimers prevent hepatitis C virus infection in cell culture

Nanomedicine. 2017 Jan;13(1):49-58. doi: 10.1016/j.nano.2016.08.018. Epub 2016 Aug 22.

Abstract

Hepatitis C virus (HCV) infection is a major biomedical problem worldwide. Although new direct antiviral agents (DAAs) have been developed for the treatment of chronic HCV infection, the potential emergence of resistant virus variants and the difficulties to implement their administration worldwide make the development of novel antiviral agents an urgent need. Moreover, no effective vaccine is available against HCV and transmission of the virus still occurs particularly when prophylactic measures are not taken. We used a cell-based system to screen a battery of polyanionic carbosilane dendrimers (PCDs) to identify compounds with antiviral activity against HCV and show that they inhibit effective virus adsorption of major HCV genotypes. Interestingly, one of the PCDs irreversibly destabilized infectious virions. This compound displays additive effect in combination with a clinically relevant DAA, sofosbuvir. Our results support further characterization of these molecules as nanotools for the control of hepatitis C virus spread.

Keywords: Antiviral; Carbosilane dendrimer; Hepatitis C virus; Nanotechnology; Virucidal.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Cell Culture Techniques
  • Cell Line
  • Dendrimers / pharmacology*
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Humans
  • Polyelectrolytes
  • Polymers / pharmacology
  • Silanes / pharmacology*
  • Virion / drug effects

Substances

  • Antiviral Agents
  • Dendrimers
  • Polyelectrolytes
  • Polymers
  • Silanes
  • carbosilane
  • polyanions