{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:45:12Z","timestamp":1777452312303,"version":"3.51.4"},"reference-count":29,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Suppression of viral replication with nucleoside\/nucleotide inhibitors has been shown to greatly improve the outcome of chronic HBV infection. (\u03b2-l-nucleoside analogues, especially \u03b2-l-deoxycytidine derivatives represent one of the most efficient groups of antiretroviral compounds. We recently described that hydroxylation of the amino group of these \u03b2-l-deoxycytidine derivatives preserved their strong HBV inhibitory activity in vitro, but strongly reduced their cytotoxicity. From this new group of compounds we selected \u03b2-l-2\u2032,3\u2032-didehydro-2\u2032,3\u2032-dideoxy-N\n                      <jats:sup>4<\/jats:sup>\n                      -hydroxy-5-fluorocytidine (l-Hyd4FC) for a first in vivo investigation. The aim of this study was to determine the antiviral activity of l-Hyd4FC in HBV-infected human liver chimeric urokinase plasminogen activator (uPA)\/SCID mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Stably infected animals (median 6x10\n                      <jats:sup>7<\/jats:sup>\n                      HBV DNA\/ ml) were injected daily with either l-Hyd4FC (50 mg\/kg) or saline as controls. Mice treated with lamivudine served to compare the in vivo antiviral potency of l-Hyd4FC. Virological changes were determined by quantitative PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment with l-Hyd4FC for 4 weeks induced a 2-log reduction of viraemia, while a median 1.5-log decline was achieved with lamivudine. Intrahepatically, l-Hyd4FC induced a median eightfold decline of viral activity (relaxed circular DNA\/covalently closed circular DNA), and threefold reduction of pregenomic RNA\/GAPDH levels. No significant decline of subgenomic HBV transcripts, as well as of circulating hepatitis B e antigen and hepatitis B surface antigen was detected. Maintenance of human serum albumin concentrations throughout the study, negative TUNEL staining and occurrence of viral rebound after drug withdrawal indicated that l-Hyd4FC was not toxic in human hepatocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Administration of l-Hyd4FC in uPA\/SCID mice harbouring HBV-infected human hepatocytes demonstrated the high antiviral potency of this drug in vivo. Such characteristics make l-Hyd4FC a good candidate for further investigations a as potential HBV therapeutic agent.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp2075","type":"journal-article","created":{"date-parts":[[2012,2,27]],"date-time":"2012-02-27T06:58:42Z","timestamp":1330325922000},"page":"623-631","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Strong Antiviral Activity of the New L-Hydroxycytidine Derivative,\n                    <scp>L<\/scp>\n                    -HYD4FC, In HBV-Infected Human Chimeric UPA\/SCID Mice"],"prefix":"10.1177","volume":"17","author":[{"given":"Tassilo","family":"Volz","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University Medical Center Hamburg, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"L\u00fctgehetmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Medical Center Hamburg, Hamburg, Germany"},{"name":"Department of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena","family":"Allweiss","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Medical Center Hamburg, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Warlich","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Medical Center Hamburg, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanette","family":"Bierwolf","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg M","family":"Pollok","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg","family":"Petersen","sequence":"additional","affiliation":[{"name":"IFI Institute for Interdisciplinary Medicine at Asklepios Clinic St Georg, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eckart","family":"Matthes","sequence":"additional","affiliation":[{"name":"Max-Delbr\u00fcck-Centrum for Molecular Medicine, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maura","family":"Dandri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Medical Center Hamburg, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2012,5,1]]},"reference":[{"key":"bibr1-IMP2075","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.12.003"},{"key":"bibr2-IMP2075","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.08.063"},{"key":"bibr3-IMP2075","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.12.9392-9399.1997"},{"key":"bibr4-IMP2075","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2000.8701"},{"key":"bibr5-IMP2075","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23611"},{"key":"bibr6-IMP2075","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00001-07"},{"key":"bibr7-IMP2075","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01176-09"},{"key":"bibr8-IMP2075","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90615-6"},{"key":"bibr9-IMP2075","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20657"},{"key":"bibr10-IMP2075","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63352-4"},{"key":"bibr11-IMP2075","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00200.2010"},{"key":"bibr12-IMP2075","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.23314"},{"key":"bibr13-IMP2075","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1389"},{"key":"bibr14-IMP2075","doi-asserted-by":"publisher","DOI":"10.1038\/90968"},{"key":"bibr15-IMP2075","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20892"},{"key":"bibr16-IMP2075","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.09.002"},{"key":"bibr17-IMP2075","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2008.07.006"},{"key":"bibr18-IMP2075","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22469"},{"key":"bibr19-IMP2075","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.28189"},{"key":"bibr20-IMP2075","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.02.057"},{"key":"bibr21-IMP2075","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.06.057"},{"key":"bibr22-IMP2075","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-939760"},{"key":"bibr23-IMP2075","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22547"},{"key":"bibr24-IMP2075","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.09.021"},{"key":"bibr25-IMP2075","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.03.018"},{"key":"bibr26-IMP2075","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21282"},{"key":"bibr27-IMP2075","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1177\/135965350801300106","volume":"13","author":"Lutgehetmann 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