{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T16:16:49Z","timestamp":1768407409777,"version":"3.49.0"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic hepatitis B virus (HBV) infection remains a significant global health challenge due to its link to severe conditions like HBV\u2010related cirrhosis and hepatocellular carcinoma (HCC). Although current treatments effectively reduce viral levels, they have limited impact on certain HBV elements, namely hepatitis B surface antigen (HBsAg) and covalently closed circular DNA (cccDNA). This highlights the urgent need for innovative pharmaceutical and biological interventions that can disrupt HBsAg production originating from cccDNA. In this study, we identified a natural furanocoumarin compound, Imperatorin, which markedly inhibited the expression of HBsAg from cccDNA, by screening a library of natural compounds derived from Chinese herbal medicines using ELISA assay and qRT\u2010PCR. The pharmacodynamics study of Imperatorin was explored on HBV infected HepG2\u2010NTCP\/PHHs and HBV\u2010infected humanized mouse model. Proteome analysis was performed on HBV infected HepG2\u2010NTCP cells following Imperatorin treatment. Molecular docking and bio\u2010layer interferometry (BLI) were used for finding the target of Imperatorin. Our findings demonstrated Imperatorin remarkably reduced the level of HBsAg, HBV RNAs, HBV DNA\u00a0and transcriptional activity of cccDNA both in vitro and in vivo. Additionally, Imperatorin effectively restrained the actions of HBV promoters responsible for cccDNA transcription. Mechanistic study revealed that Imperatorin directly binds to ERK and subsequently interfering with the activation of CAMP response element\u2010binding protein (CREB), a crucial transcriptional factor for HBV and has been demonstrated to bind to the PreS2\/S and X promoter regions of HBV. Importantly, the absence of ERK could nullify the antiviral impact triggered by Imperatorin. Collectively, the natural compound Imperatorin may be an effective candidate agent for inhibiting HBsAg production and cccDNA transcription by impeding the activities of HBV promoters through ERK\u2010CREB axis.<\/jats:p>","DOI":"10.1002\/jmv.29669","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T01:48:56Z","timestamp":1716342536000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Discovery and mechanistic study of Imperatorin that inhibits HBsAg expression and cccDNA transcription"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4036-5870","authenticated-orcid":false,"given":"Fang","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Chongqing Hospital of Traditional Chinese Medicine  Chongqing China"},{"name":"Chongqing Key Laboratory of Sichuan\u2010Chongqing Co\u2010construction for Diagnosis and 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