{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:41:00Z","timestamp":1790091660234,"version":"4.0.1"},"reference-count":72,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["MA1289\/7-3_TS87\/16-3"],"award-info":[{"award-number":["MA1289\/7-3_TS87\/16-3"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Training Group GRK2504 (DFG)","award":["subproject A1"],"award-info":[{"award-number":["subproject A1"]}]},{"DOI":"10.13039\/501100002745","name":"Bayerische Forschungsstiftung","doi-asserted-by":"publisher","award":["DeeP-CMV\/AP-5\/MM"],"award-info":[{"award-number":["DeeP-CMV\/AP-5\/MM"]}],"id":[{"id":"10.13039\/501100002745","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Johannes und Frieda Marohn-Stiftung","award":["Alz\/Iko-Hahn\/2019"],"award-info":[{"award-number":["Alz\/Iko-Hahn\/2019"]}]},{"name":"Wilhelm Sander-Stiftung (WSS)","award":["MA\/SBT 2018.121.1"],"award-info":[{"award-number":["MA\/SBT 2018.121.1"]}]},{"name":"Interdisciplinary Center for Clinical Research of the FAU Erlangen-N\u00fcrnberg","award":["IZKF-A88"],"award-info":[{"award-number":["IZKF-A88"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human cytomegalovirus (HCMV) is a human pathogenic herpesvirus associated with a variety of clinical symptoms. Current antiviral therapy is not always effective, so that improved drug classes and drug-targeting strategies are needed. Particularly host-directed antivirals, including pharmaceutical kinase inhibitors (PKIs), may help to overcome problems of drug resistance. Here, we focused on utilizing a selection of clinically relevant PKIs and determined their anticytomegaloviral efficacies. Particularly, PKIs directed to host or viral cyclin-dependent kinases, i.e., abemaciclib, LDC4297 and maribavir, exerted promising profiles against human and murine cytomegaloviruses. The anti-HCMV in vitro activity of the approved anti-cancer drug abemaciclib was confirmed in vivo using our luciferase-based murine cytomegalovirus (MCMV) animal model in immunocompetent mice. To assess drug combinations, we applied the Bliss independence checkerboard and Loewe additivity fixed-dose assays in parallel. Results revealed that (i) both affirmative approaches provided valuable information on anti-CMV drug efficacies and interactions, (ii) the analyzed combinations comprised additive, synergistic or antagonistic drug interactions consistent with the drugs\u2019 antiviral mode-of-action, (iii) the selected PKIs, especially LDC4297, showed promising inhibitory profiles, not only against HCMV but also other \u03b1-, \u03b2- and \u03b3-herpesviruses, and specifically, (iv) the combination treatment with LDC4297 and maribavir revealed a strong synergism against HCMV, which might open doors towards novel clinical options in the near future. Taken together, this study highlights the potential of therapeutic drug combinations of current developmental\/preclinical PKIs.<\/jats:p>","DOI":"10.3390\/ijms22020575","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T19:55:56Z","timestamp":1610308556000},"page":"575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Combinatorial Drug Treatments Reveal Promising Anticytomegaloviral Profiles for Clinically Relevant Pharmaceutical Kinase Inhibitors (PKIs)"],"prefix":"10.3390","volume":"22","author":[{"given":"Markus","family":"Wild","sequence":"first","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), Schlossgarten 4, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintawee","family":"Kicuntod","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), Schlossgarten 4, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Seyler","sequence":"additional","affiliation":[{"name":"Institute of Radiology, University Medical Center Erlangen, FAU, Palmsanlage 5, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Wangen","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), Schlossgarten 4, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0698-5395","authenticated-orcid":false,"given":"Luca D.","family":"Bertzbach","sequence":"additional","affiliation":[{"name":"Institute of Virology, Freie Universit\u00e4t Berlin, Robert-von-Ostertag-Stra\u00dfe 7-13, 14163 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9975-0642","authenticated-orcid":false,"given":"Andel\u00e9 M.","family":"Conradie","sequence":"additional","affiliation":[{"name":"Institute of Virology, Freie Universit\u00e4t Berlin, Robert-von-Ostertag-Stra\u00dfe 7-13, 14163 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-2695","authenticated-orcid":false,"given":"Benedikt B.","family":"Kaufer","sequence":"additional","affiliation":[{"name":"Institute of Virology, Freie Universit\u00e4t Berlin, Robert-von-Ostertag-Stra\u00dfe 7-13, 14163 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), Schlossgarten 4, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlef","family":"Michel","sequence":"additional","affiliation":[{"name":"Institute for Virology, Ulm University Medical Center, Albert-Einstein-Allee 11, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5537-438X","authenticated-orcid":false,"given":"Jan","family":"Eickhoff","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH, Otto-Hahn-Str. 15, 44227 Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4845-0951","authenticated-orcid":false,"given":"Svetlana B.","family":"Tsogoeva","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry I, FAU, Nikolaus-Fiebiger-Stra\u00dfe 10, 91058 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"B\u00e4uerle","sequence":"additional","affiliation":[{"name":"Institute of Radiology, University Medical Center Erlangen, FAU, Palmsanlage 5, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3011-8416","authenticated-orcid":false,"given":"Friedrich","family":"Hahn","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), Schlossgarten 4, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Marschall","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), Schlossgarten 4, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/rmv.655","article-title":"Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection","volume":"20","author":"Cannon","year":"2010","journal-title":"Rev. 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