title: GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses.
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.
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Lo
authors.affiliation: Gilead Sciences, Inc. Foster City, California, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Jordan
authors.affiliation: Gilead Sciences, Inc. Foster City, California, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Arvey
authors.affiliation: Gilead Sciences, Inc. Foster City, California, USA.
authors.forename: Jawahar
authors.initials: J
authors.lastname: Sudhamsu
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Punya
authors.initials: P
authors.lastname: Shrivastava-Ranjan
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Hotard
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Flint
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Laura K
authors.initials: LK
authors.lastname: McMullan
authors.affiliation: Gilead Sciences, Inc. Foster City, California, USA.
authors.forename: Dustin
authors.initials: D
authors.lastname: Siegel
authors.affiliation: Gilead Sciences, Inc. Foster City, California, USA.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Clarke
authors.affiliation: Gilead Sciences, Inc. Foster City, California, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Mackman
authors.affiliation: Gilead Sciences, Inc. Foster City, California, USA.
authors.forename: Hon C
authors.initials: HC
authors.lastname: Hui
authors.affiliation: Gilead Sciences, Inc. Foster City, California, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Perron
authors.affiliation: Gilead Sciences, Inc. Foster City, California, USA.
authors.forename: Adrian S
authors.initials: AS
authors.lastname: Ray
authors.affiliation: Gilead Sciences, Inc. Foster City, California, USA.
authors.forename: Tomas
authors.initials: T
authors.lastname: Cihlar
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Nichol
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Christina F
authors.initials: CF
authors.lastname: Spiropoulou
mesh_terms: D000072283:A549 Cells; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives; D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D015870:Gene Expression; D057809:HEK293 Cells; D006367:HeLa Cells; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D029024:Marburgvirus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D009705:Nucleosides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D010252:Paramyxoviridae / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D018099:Pneumovirinae / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D011355:Prodrugs / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012265:Ribonucleotides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D014709:Vero Cells; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D011355:Prodrugs; D012265:Ribonucleotides; D014764:Viral Proteins; C000606551:remdesivir; D000249:Adenosine Monophosphate; D012324:RNA-Dependent RNA Polymerase; D000409:Alanine