{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:20:46Z","timestamp":1772252446342,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T00:00:00Z","timestamp":1576800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Frankfurter Stiftung f\u00fcr krebskranke Kinder","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"Hilfe fuer krebskranke Kinder Frankfurt e.V.","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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 disease.<\/jats:p>","DOI":"10.3390\/cells9010031","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T03:23:12Z","timestamp":1577071392000},"page":"31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Thrombopoietin Receptor Agonist Eltrombopag Inhibits Human Cytomegalovirus Replication Via Iron Chelation"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9773-3881","authenticated-orcid":false,"given":"Jens-Uwe","family":"Vogel","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Medizinische Virologie, Universit\u00e4tsklinikum, Goethe-Universit\u00e4t, Paul Ehrlich-Str. 40, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Virologie, Universit\u00e4tsklinikum, Goethe-Universit\u00e4t, Paul Ehrlich-Str. 40, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Virologie, Universit\u00e4tsklinikum, Goethe-Universit\u00e4t, Paul Ehrlich-Str. 40, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Rothweiler","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Virologie, Universit\u00e4tsklinikum, Goethe-Universit\u00e4t, Paul Ehrlich-Str. 40, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Koch","sequence":"additional","affiliation":[{"name":"Medizinische Klinik III, Nephrologie, Klinikum der Goethe-Universit\u00e4t, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8113-3312","authenticated-orcid":false,"given":"Patrick","family":"Baer","sequence":"additional","affiliation":[{"name":"Medizinische Klinik III, Nephrologie, Klinikum der Goethe-Universit\u00e4t, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Rabenau","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Virologie, Universit\u00e4tsklinikum, Goethe-Universit\u00e4t, Paul Ehrlich-Str. 40, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Detlef","family":"Michel","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Virologie, Universit\u00e4tsklinikum Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9878-3119","authenticated-orcid":false,"given":"Thomas","family":"Stamminger","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Virologie, Universit\u00e4tsklinikum Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5710-5888","authenticated-orcid":false,"given":"Martin","family":"Michaelis","sequence":"additional","affiliation":[{"name":"Industry Biotechnology Centre and School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5710-5888","authenticated-orcid":false,"given":"Jindrich","family":"Cinatl","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Virologie, Universit\u00e4tsklinikum, Goethe-Universit\u00e4t, Paul Ehrlich-Str. 40, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1177\/2040620717693573","article-title":"From chronic immune thrombocytopenia to severe aplastic anemia: Recent insights into the evolution of eltrombopag","volume":"8","author":"Gill","year":"2017","journal-title":"Ther. 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