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Sci Rep ; 7: 43395, 2017 03 06.
Article in English | MEDLINE | ID: mdl-28262699

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.


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