TY  - JOUR
A1  - Vogel, Jens-Uwe
A1  - Schmidt, Sophie Marion
A1  - Schmidt, Daniel
A1  - Rothweiler, Florian
A1  - Koch, Benjamin Florian
A1  - Baer, Patrick C.
A1  - Rabenau, Holger
A1  - Michel, Detlef
A1  - Stamminger, Thomas
A1  - Michaelis, Martin
A1  - Cinatl, Jindrich
T1  - The thrombopoietin receptor agonist eltrombopag inhibits human cytomegalovirus replication via iron chelation
T2  - Cells
N2  - 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 Fe3+ prevented the anti-HCMV effects, indicating that it inhibits HCMV replication via iron chelation. This may be of particular interest for the treatment of cytopenias after hematopoietic stem cell transplantation, as HCMV reactivation is a major reason for transplantation failure. Since therapeutic eltrombopag concentrations are effective against drug-resistant viruses, and synergistically increase the effects of ganciclovir, eltrombopag is also a drug-repurposing candidate for the treatment of therapy-refractory HCMV diseas.
KW  - human cytomegalovirus
KW  - antiviral therapy
KW  - eltrombopag
KW  - thrombopietin receptor agonist
KW  - drug resistance
KW  - iron chelation
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/52760
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-527603
SN  - 2073-4409
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
VL  - 9
IS  - 1, Art. 31
SP  - 1
EP  - 12
PB  - MDPI
CY  - Basel
ER  -