{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T07:25:54Z","timestamp":1768634754149,"version":"3.49.0"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,4,25]],"date-time":"2013-04-25T00:00:00Z","timestamp":1366848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Nature Scientific Foundation","award":["30872224"],"award-info":[{"award-number":["30872224"]}]},{"name":"National Nature Scientific Foundation","award":["81071366"],"award-info":[{"award-number":["81071366"]}]},{"name":"Scientific and Technological Hall of Guangdong Province","award":["2009B030801084"],"award-info":[{"award-number":["2009B030801084"]}]},{"name":"Scientific and Technological Hall of Guangdong Province","award":["10251008901000018"],"award-info":[{"award-number":["10251008901000018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Hepatitis B e antigen (<jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg) is essential for the development of chronic hepatitis B virus (<jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>) infection. Furin, a proprotein convertase, plays a key role in processing of <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg precursor into maturated <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg. For these reasons, the therapeutic potential of furin inhibition for chronic <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> infection was studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effects of furin inhibitor I (decanoyl\u2010<jats:styled-content style=\"fixed-case\">RVKR<\/jats:styled-content>\u2010chloromethylketone, <jats:styled-content style=\"fixed-case\">CMK<\/jats:styled-content>) and furin inhibitor II (hexa\u2010D\u2010arginine, D6R) on <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg secretion, the destination of unprocessed precursor and cellular secretory functions were comparatively investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">CMK<\/jats:styled-content> and D6R significantly decreased the supernatant level of <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg and increased the intracellular level of <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg precursor in HepG2.2.15 cells <jats:italic>in vitro<\/jats:italic>. The accumulated <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg precursor was not found to be retro\u2010transported into the cytosol to inhibit <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> replication as expected, but was found to be expressed on the cell surface, where it may be more convenient to mediate host immune responses. Furthermore, these inhibitors at effective concentrations were not found to interfere with the maturations of albumin and prothrombin. Compared with <jats:styled-content style=\"fixed-case\">CMK<\/jats:styled-content>, D6R was suboptimal in effectiveness; however, D6R neither enhanced <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> replication through the accumulation of cytosolic <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>cAg nor did it cause severe cell damage in an elongated safety analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Furin inhibitors <jats:styled-content style=\"fixed-case\">CMK<\/jats:styled-content> and D6R reduce <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg secretion and increase cell surface expression of the <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg precursor in HepG2.2.15 cells. Novel furin inhibitors or modified forms of D6R may promote the reduction of immune tolerance and the elimination of infected hepatocytes in patients with chronic <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> infection.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12185","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T08:37:15Z","timestamp":1365064635000},"page":"1230-1238","source":"Crossref","is-referenced-by-count":15,"title":["Therapeutic potential of furin inhibitors for the chronic infection of hepatitis B virus"],"prefix":"10.1111","volume":"33","author":[{"given":"Yan J.","family":"Pang","sequence":"first","affiliation":[{"name":"Hepatology Laboratory The Hospital for Liver Disease Sun Yat\u2010Sen University Guangzhou China"},{"name":"Department of Infectious Diseases The Third Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao J.","family":"Tan","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory The Hospital for Liver Disease Sun Yat\u2010Sen University Guangzhou China"},{"name":"Department of Infectious Diseases The Third Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong M.","family":"Li","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory The Hospital for Liver Disease Sun Yat\u2010Sen University Guangzhou China"},{"name":"Department of Infectious Diseases The Third Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi H.","family":"Zheng","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory The Hospital for Liver Disease Sun Yat\u2010Sen University Guangzhou China"},{"name":"Department of Infectious Diseases The Third Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui X.","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases The Third Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao M.","family":"Peng","sequence":"additional","affiliation":[{"name":"Hepatology Laboratory The Hospital for Liver Disease Sun Yat\u2010Sen University Guangzhou China"},{"name":"Liver Disease Key Laboratory of Guangdong Province Guangzhou 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