GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses

Sci Rep. 2017 Mar 6;7:43395. doi: 10.1038/srep43395.

Abstract

GS-5734 is a monophosphate prodrug of an adenosine nucleoside analog that showed therapeutic efficacy in a non-human primate model of Ebola virus infection. It has been administered under compassionate use to two Ebola patients, both of whom survived, and is currently in Phase 2 clinical development for treatment of Ebola virus disease. Here we report the antiviral activities of GS-5734 and the parent nucleoside analog across multiple virus families, providing evidence to support new indications for this compound against human viruses of significant public health concern.

Publication types

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

MeSH terms

  • A549 Cells
  • Alanine / analogs & derivatives*
  • Alanine / chemical synthesis
  • Alanine / metabolism
  • Alanine / pharmacology
  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology*
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Ebolavirus / drug effects*
  • Ebolavirus / enzymology
  • Ebolavirus / growth & development
  • Gene Expression
  • HEK293 Cells
  • HeLa Cells
  • Hepatocytes / drug effects
  • Hepatocytes / virology
  • Humans
  • Marburgvirus / drug effects*
  • Marburgvirus / enzymology
  • Marburgvirus / growth & development
  • Microbial Sensitivity Tests
  • Nucleosides / chemical synthesis
  • Nucleosides / metabolism
  • Nucleosides / pharmacology
  • Paramyxoviridae / drug effects*
  • Paramyxoviridae / enzymology
  • Paramyxoviridae / growth & development
  • Pneumovirinae / drug effects*
  • Pneumovirinae / enzymology
  • Pneumovirinae / growth & development
  • Prodrugs / chemical synthesis
  • Prodrugs / metabolism
  • Prodrugs / pharmacology*
  • RNA Replicase / antagonists & inhibitors
  • RNA Replicase / chemistry
  • RNA Replicase / genetics
  • RNA Replicase / metabolism
  • Ribonucleotides / chemical synthesis
  • Ribonucleotides / metabolism
  • Ribonucleotides / pharmacology*
  • Vero Cells
  • Viral Proteins / antagonists & inhibitors
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • Antiviral Agents
  • Nucleosides
  • Prodrugs
  • Ribonucleotides
  • Viral Proteins
  • remdesivir
  • RNA Replicase
  • Alanine