The Thrombopoietin Receptor Agonist Eltrombopag Inhibits Human Cytomegalovirus Replication Via Iron Chelation.
Animals
Benzoates
/ pharmacology
Cells, Cultured
Cytomegalovirus
/ drug effects
Drug Synergism
Fibroblasts
/ cytology
Ganciclovir
/ pharmacology
Humans
Hydrazines
/ pharmacology
Iron Chelating Agents
/ pharmacology
Mesenchymal Stem Cells
/ cytology
Mice
NIH 3T3 Cells
Pyrazoles
/ pharmacology
Virus Replication
/ drug effects
antiviral therapy
drug resistance
eltrombopag
human cytomegalovirus
iron chelation
thrombopietin receptor agonist
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
20 12 2019
20 12 2019
Historique:
received:
01
11
2019
revised:
12
12
2019
accepted:
18
12
2019
entrez:
22
12
2019
pubmed:
22
12
2019
medline:
28
8
2020
Statut:
epublish
Résumé
The thrombopoietin receptor agonist eltrombopag was successfully used against human cytomegalovirus (HCMV)-associated thrombocytopenia refractory to immunomodulatory and antiviral drugs. These effects were ascribed to the effects of eltrombopag on megakaryocytes. Here, we tested whether eltrombopag may also exert direct antiviral effects. Therapeutic eltrombopag concentrations inhibited HCMV replication in human fibroblasts and adult mesenchymal stem cells infected with six different virus strains and drug-resistant clinical isolates. Eltrombopag also synergistically increased the anti-HCMV activity of the mainstay drug ganciclovir. Time-of-addition experiments suggested that eltrombopag interfered with HCMV replication after virus entry. Eltrombopag was effective in thrombopoietin receptor-negative cells, and the addition of Fe
Identifiants
pubmed: 31861948
pii: cells9010031
doi: 10.3390/cells9010031
pmc: PMC7017049
pii:
doi:
Substances chimiques
Benzoates
0
Hydrazines
0
Iron Chelating Agents
0
Pyrazoles
0
Ganciclovir
P9G3CKZ4P5
eltrombopag
S56D65XJ9G
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Frankfurter Stiftung für krebskranke Kinder
ID : n/a
Pays : International
Organisme : Hilfe fuer krebskranke Kinder Frankfurt e.V.
ID : n/a
Pays : International
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
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