{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:23:31Z","timestamp":1790785411256,"version":"4.1.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Chronic HBV infection is a major health problem worldwide. Currently, the first\u2010line treatment for HBV is nucleos(t)ide analogs or interferons; however, efficient therapeutic approaches that enable cure are lacking. Therefore, anti\u2010HBV agents with mechanisms distinct from those of current drugs are needed. Sodium taurocholate cotransporting polypeptide (NTCP) was previously identified as an HBV receptor that is inhibited by several compounds. Farnesoid X receptor (FXR) activation also inhibits NTCP function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>In this study, we investigated the inhibitory effect of bile acid (BA) derivatives\u2014namely obeticholic acid (OCA), 6\u03b1\u2010ethyl\u201024\u2010nor\u20105\u03b2\u2010cholane\u20103\u03b1,7\u03b1,23\u2010triol\u201023 sulfate sodium salt (INT\u2010767; a dual agonist of FXR and Takeda G protein\u2010coupled receptor [TGR5]), and 6\u03b1\u2010ethyl\u201023(S)\u2010methyl\u2010cholic acid (INT\u2010777; a TGR5 agonist)\u20143\u2010(2,6\u2010dichlorophenyl)\u20104\u2010(3\u2032\u2010carboxy\u20102\u2010chlorostilben\u20104\u2010yl)oxymethyl\u20105\u2010isopropylisoxazole (GW4064; a FXR agonist), cyclosporin A, and irbesartan. OCA and INT\u2010777 suppressed HBV infection in HepG2\u2010human NTCP\u2010C4 cells. Interestingly, INT\u2010767 showed potent inhibition by attaching to HBV particles rather than binding to NTCP. As an entry inhibitor, INT\u2010767 was stronger than various natural BAs. Furthermore, in chimeric mice with humanized liver, INT\u2010767 markedly delayed the initial rise of HBsAg, HBeAg, and HBV DNA and reduced covalently closed circular DNA. The strong inhibitory effect of INT\u2010767 may be due to the cumulative effect of its ability to inhibit the entry of HBV and to stimulate FXR downstream signaling, which affects the postentry step.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results suggest that BA derivatives, particularly INT\u2010767, are prospective candidate anti\u2010HBV agents. Clarifying the underlying mechanisms of BA derivatives would facilitate the development of anti\u2010HBV agents.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.31712","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T04:54:37Z","timestamp":1610686477000},"page":"83-98","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":42,"title":["Dual Agonist of Farnesoid X Receptor and Takeda G Protein\u2010Coupled Receptor 5 Inhibits Hepatitis B Virus Infection In Vitro and In Vivo"],"prefix":"10.1097","volume":"74","author":[{"given":"Kiyoaki","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Gastroenterology,Aichi Medical University,Nagakute,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Okumura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Aichi Medical 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