{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T18:32:31Z","timestamp":1772821951818,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012781","name":"Merck Sharp and Dohme K.K.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Letermovir and ganciclovir are used to prevent cytomegalovirus (CMV) infection, but the generation of resistant viruses and the interactions between wild and resistant CMV have not been studied. We evaluated the effect of letermovir\/ganciclovir on the release of the wild\u2010type and letermovir\/ganciclovir\u2010resistant CMV in their coinfected or superinfected cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>We analysed the extracellular CMV infectivity released from CMV\u2010infected cells treated with letermovir and ganciclovir. Subsequently, we characterized growth of letermovir\/ganciclovir\u2010resistant viruses in wild\u2010type CMV\u2010infected cells in the presence of letermovir\/ganciclovir, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      The number of infectious cells resuming viral replication after letermovir\/ganciclovir removal decreased over time, and the CMV\u2010infected cells treated with letermovir or ganciclovir remained infectious for 1\u2009month. During the treatment course, letermovir\u2010\/ganciclovir\u2010resistant viruses arise from CMV infection foci, and we investigated the proliferation of resistant viruses in the presence of letermovir\/ganciclovir. Letermovir inhibited superinfected CMV release by inhibiting the superinfected CMV from using the DNA terminase\u2010packaging complex pathway occupied by a prior infected CMV. Co\u2010infection and superinfection of ganciclovir\u2010resistant CMV in wild\u2010type CMV\u2010infected cells inhibited viral release by inhibiting DNA synthesis by ganciclovir phosphorylated by wild\u2010type\n                      <jats:italic>UL97<\/jats:italic>\n                      . These results suggested that letermovir\u2010resistant CMV emerging in wild\u2010type CMV\u2010infected cells would not easily spread to the surrounding wild\u2010type CMV\u2010infected cells in CMV\u2010infected patients under letermovir.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Despite different mechanisms of action, both drugs inhibited the spread of newly emerging resistant viruses around wild\u2010type CMV\u2010infected lesions during letermovir\/ganciclovir treatment, suggesting the practical use of both drugs and strategies for treating drug\u2010resistant CMV.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70239","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T14:13:07Z","timestamp":1763129587000},"page":"1171-1185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mechanistic insights into the inhibition of drug\u2010resistant cytomegalovirus by letermovir and ganciclovir"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7721-9359","authenticated-orcid":false,"given":"Noriaki","family":"Sato","sequence":"first","affiliation":[{"name":"Division of Health Medical Intelligence, Human Genome Center, The Institute of Medical Science The University of Tokyo  Tokyo Japan"},{"name":"Department of Nephrology, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuko","family":"Shiraki","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tohru","family":"Daikoku","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Pharmaceutical Sciences Hokuriku University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaya","family":"Takemoto","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Pharmaceutical Sciences Hokuriku University  Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinori","family":"Takemura","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Toyama Nishi General Hospital  Toyama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaoru","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiya","family":"Imoto","sequence":"additional","affiliation":[{"name":"Division of Health Medical Intelligence, Human Genome Center, The Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motoko","family":"Yanagita","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazunari","family":"Tanabe","sequence":"additional","affiliation":[{"name":"Kidney Transplant Center Shonan Kamakura General Hospital  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimiyasu","family":"Shiraki","sequence":"additional","affiliation":[{"name":"Faculty of Nursing Senri Kinran University  Suita Osaka Japan"},{"name":"Hokuriku Health Service Association  Toyama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2016.0151"},{"issue":"2","key":"e_1_2_12_3_1","first-page":"S289","article-title":"The concise guide to PHARMACOLOGY 2023\/24: Enzymes","volume":"180","author":"Alexander S. 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