{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T05:19:33Z","timestamp":1781932773784,"version":"3.54.5"},"reference-count":26,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"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":[[2012,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>HBV infection causes major public health problems worldwide. The clinical limitation of current antiviral drugs for HBV, such as lamivudine, is causing rapid emergence of drug-resistant viral strains during prolonged antiviral therapy. Therefore, new antiviral drugs are urgently needed to prevent or delay the selection of drug-resistant HBV mutants. A novel cytidine analogue, FNC (2\u2032-deoxy-2\u2032-\u03b2-fluoro-4\u2032-azidocytidine), was recently shown to strongly inhibit human HBV and duck HBV (DHBV) replication in vitro and in vivo, respectively. The present study was designed to evaluate the in vitro antiviral activity of FNC against clinical wild-type and lamivudine-resistant HBV isolates in transiently transfected cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      HBV DNA was extracted from serum samples collected both before lamivudine therapy and at the time of viral breakthrough and was amplified by PCR. The amplicon was cloned into a novel expression vector, pHY106, which can initiate the intracellular HBV replication cycle after cell transfection. Following transfection of the cloned amplicon into HepG2 cells, a drug susceptibility assay was performed. Quantitative real-time PCR was used for determining the amount of intracellular HBV DNA, and the effective concentration required to reduce HBV replication by 50% (EC\n                      <jats:sub>50<\/jats:sub>\n                      ) was calculated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      FNC inhibited the replication of both wild-type and lamivudine-resistant HBV clinical isolates in a dose-dependent manner, with mean \u00b1sd EC\n                      <jats:sub>50<\/jats:sub>\n                      values of 0.12 \u00b10.01 \u03bcM and 0.27 \u00b10.01 \u03bcM, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>FNC is a potential antiviral agent against both wild-type and lamivudine-resistant HBV clinical isolates, and therefore deserves further evaluation for the treatment of HBV infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp2292","type":"journal-article","created":{"date-parts":[[2012,8,9]],"date-time":"2012-08-09T06:55:26Z","timestamp":1344495326000},"page":"1593-1599","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":32,"title":["Novel Nucleoside Analogue Fnc is Effective against Both Wild-Type and Lamivudine-Resistant HBV Clinical Isolates"],"prefix":"10.1177","volume":"17","author":[{"given":"Yubing","family":"Zhou","sequence":"first","affiliation":[{"name":"Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China"},{"name":"School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China"},{"name":"The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoang","family":"Yang","sequence":"additional","affiliation":[{"name":"Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"The College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyu","family":"Sun","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Jiang","sequence":"additional","affiliation":[{"name":"Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Yang","sequence":"additional","affiliation":[{"name":"The College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingduan","family":"Wang","sequence":"additional","affiliation":[{"name":"Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbiao","family":"Chang","sequence":"additional","affiliation":[{"name":"The College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,11,1]]},"reference":[{"key":"bibr1-IMP2292","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2010.06545.x"},{"key":"bibr2-IMP2292","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2010.05.005"},{"key":"bibr3-IMP2292","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24318"},{"key":"bibr4-IMP2292","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(09)70056-8"},{"key":"bibr5-IMP2292","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510270628"},{"key":"bibr6-IMP2292","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.21.11833-11841.2003"},{"key":"bibr7-IMP2292","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20984"},{"key":"bibr8-IMP2292","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1177\/135965350400900311","volume":"9","author":"Lada O.","year":"2004","journal-title":"Antivir 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United State patent US 2010\/0234584A1. 2010 September 16."},{"key":"bibr11-IMP2292","unstructured":"Chang J. 2\u2032-Fluoro-4\u2032-substituted nucleosides, the preparation and use. European patent EP 2177527. 2010 April 21."},{"key":"bibr12-IMP2292","doi-asserted-by":"crossref","unstructured":"Chang J., Bao X., Wang Q., Guo X., Wang W., Qi X. 2\u2032-Fluoro-4\u2032-substituted nucleoside analogs, synthetic method and use thereof. Chinese patent CN1014627. 2009 May 20.","DOI":"10.1016\/j.bmcl.2010.05.090"},{"key":"bibr13-IMP2292","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.06.020"},{"key":"bibr14-IMP2292","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708929200"},{"key":"bibr15-IMP2292","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2094"},{"key":"bibr16-IMP2292","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2003.07.003"},{"key":"bibr17-IMP2292","doi-asserted-by":"publisher","DOI":"10.1177\/135965350701200309"},{"key":"bibr18-IMP2292","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.9.5437-5444.1995"},{"key":"bibr19-IMP2292","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1755"},{"key":"bibr20-IMP2292","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2005.00578.x"},{"key":"bibr21-IMP2292","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.22454"},{"key":"bibr22-IMP2292","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1053\/j.gastro.2006.08.013","volume":"131","author":"Brunelle M.N.","year":"2006","journal-title":"Gastroenterology"},{"key":"bibr23-IMP2292","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01440-06"},{"key":"bibr24-IMP2292","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.9.2495-2501.2001"},{"key":"bibr25-IMP2292","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.3.955-961.2006"},{"key":"bibr26-IMP2292","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1541"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP2292","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP2292","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:51:03Z","timestamp":1777380663000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP2292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["10.3851\/IMP2292"],"URL":"https:\/\/doi.org\/10.3851\/imp2292","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11]]}}}