The lipid moiety of brincidofovir is required for in vitro antiviral activity against Ebola virus

Antiviral Res. 2016 Jan:125:71-8. doi: 10.1016/j.antiviral.2015.10.010. Epub 2015 Oct 23.

Abstract

Brincidofovir (BCV) is the 3-hexadecyloxy-1-propanol (HDP) lipid conjugate of the acyclic nucleoside phosphonate cidofovir (CDV). BCV has established broad-spectrum activity against double-stranded DNA (dsDNA) viruses; however, its activity against RNA viruses has been less thoroughly evaluated. Here, we report that BCV inhibited infection of Ebola virus in multiple human cell lines. Unlike the mechanism of action for BCV against cytomegalovirus and other dsDNA viruses, phosphorylation of CDV to the diphosphate form appeared unnecessary. Instead, antiviral activity required the lipid moiety and in vitro activity against EBOV was observed for several HDP-nucleotide conjugates.

Keywords: Antiviral therapy; Brincidofovir; Ebola; In vitro screen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Cidofovir
  • Cytosine / analogs & derivatives*
  • Cytosine / chemistry
  • Cytosine / pharmacology
  • Drug Evaluation, Preclinical / methods
  • Ebolavirus / drug effects*
  • HeLa Cells
  • Hemorrhagic Fever, Ebola / drug therapy*
  • Hemorrhagic Fever, Ebola / prevention & control
  • Hemorrhagic Fever, Ebola / virology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lipids / chemistry
  • Lipids / pharmacology
  • Male
  • Organophosphonates / chemistry*
  • Organophosphonates / pharmacology*
  • Structure-Activity Relationship
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Lipids
  • Organophosphonates
  • brincidofovir
  • Cytosine
  • Cidofovir