{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:41:18Z","timestamp":1779885678659,"version":"3.53.1"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"23","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI101820"],"award-info":[{"award-number":["AI101820"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI112318"],"award-info":[{"award-number":["AI112318"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI113971"],"award-info":[{"award-number":["AI113971"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007197","name":"HHS | U.S. Public Health Service","doi-asserted-by":"publisher","award":["AI07647"],"award-info":[{"award-number":["AI07647"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Cytomegalovirus (CMV) is a ubiquitous human pathogen that increases the morbidity and mortality of immunocompromised individuals. The current FDA-approved treatments for CMV infection are intended to be virus specific, yet they have significant adverse side effects, including nephrotoxicity and hematological toxicity. Thus, there is a medical need for safer and more effective CMV therapeutics. Using a high-content screen, we identified the cardiac glycoside convallatoxin as an effective compound that inhibits CMV infection. Using a panel of cardiac glycoside variants, we assessed the structural elements critical for anti-CMV activity by both experimental and\n            <jats:italic>in silico<\/jats:italic>\n            methods. Analysis of the antiviral effects, toxicities, and pharmacodynamics of different variants of cardiac glycosides identified the mechanism of inhibition as reduction of methionine import, leading to decreased immediate-early gene translation without significant toxicity. Also, convallatoxin was found to dramatically reduce the proliferation of clinical CMV strains, implying that its mechanism of action is an effective strategy to block CMV dissemination. Our study has uncovered the mechanism and structural elements of convallatoxin, which are important for effectively inhibiting CMV infection by targeting the expression of immediate-early genes.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Cytomegalovirus is a highly prevalent virus capable of causing severe disease in certain populations. The current FDA-approved therapeutics all target the same stage of the viral life cycle and induce toxicity and viral resistance. We identified convallatoxin, a novel cell-targeting antiviral that inhibits CMV infection by decreasing the synthesis of viral proteins. At doses low enough for cells to tolerate, convallatoxin was able to inhibit primary isolates of CMV, including those resistant to the anti-CMV drug ganciclovir. In addition to identifying convallatoxin as a novel antiviral, limiting mRNA translation has a dramatic impact on CMV infection and proliferation.\n          <\/jats:p>","DOI":"10.1128\/jvi.01050-16","type":"journal-article","created":{"date-parts":[[2016,9,22]],"date-time":"2016-09-22T02:29:21Z","timestamp":1474511361000},"page":"10715-10727","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Convallatoxin-Induced Reduction of Methionine Import Effectively Inhibits Human Cytomegalovirus Infection and Replication"],"prefix":"10.1128","volume":"90","author":[{"given":"Tobias","family":"Cohen","sequence":"first","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Williams","sequence":"additional","affiliation":[{"name":"Microbiotix Inc. Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Opperman","sequence":"additional","affiliation":[{"name":"Microbiotix Inc. Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"},{"name":"Experimental Therapeutics Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nell S.","family":"Lurain","sequence":"additional","affiliation":[{"name":"Department of Immunology-Microbiology, Rush University, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Tortorella","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-198503000-00003"},{"key":"e_1_3_2_3_2","first-page":"2702","volume-title":"Fields virology","author":"Mocarski ES","year":"2006","unstructured":"Mocarski ES, Shenk T, Pass RF. 2006. 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