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Article: Unique antiviral mechanism discovered in anti-hepatitis B virus research with a natural product analogue

TitleUnique antiviral mechanism discovered in anti-hepatitis B virus research with a natural product analogue
Authors
Issue Date2007
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2007, v. 104 n. 20, p. 8526-8531 How to Cite?
AbstractHelioxanthin is a natural product that inhibits the replication of a number of viruses. We found that a previously undescribed helioxanthin analogue, 8-1, exhibited potent anti-hepatitis B virus (HBV) activity with little cytotoxicity. 8-1 suppressed both HBV RNA and protein expression, as well as DNA replication of both wildtype and 3TC-resistant virus. Time-course analyses revealed that RNA expression was blocked first after treatment with 8-1, followed by viral proteins, and then DNA. 8-1 inhibited the activity of all HBV promoters by decreasing the binding of hepatocyte nuclear factor 4 (HNF-4), HNF-3, and fetoprotein factor to the precore/core promoter enhancer II region. The amount of HNF-4 and HNF-3 was decreased posttranscriptionally by 8-1 in HBV-producing cells, but not in HBV-negative cells. Therefore, 8-1 suppresses HBV replication by posttranscriptional down-regulation of critical transcription factors in HBV-producing cells, thus diminishing HBV promoter activity and blocking viral gene expression and replication. This mechanism is unique and different from other anti-HBV compounds previously described. © 2007 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/168124
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYing, Cen_US
dc.contributor.authorLi, Yen_US
dc.contributor.authorLeung, CHen_US
dc.contributor.authorRobek, MDen_US
dc.contributor.authorCheng, YCen_US
dc.date.accessioned2012-10-08T03:15:21Z-
dc.date.available2012-10-08T03:15:21Z-
dc.date.issued2007en_US
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2007, v. 104 n. 20, p. 8526-8531en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/168124-
dc.description.abstractHelioxanthin is a natural product that inhibits the replication of a number of viruses. We found that a previously undescribed helioxanthin analogue, 8-1, exhibited potent anti-hepatitis B virus (HBV) activity with little cytotoxicity. 8-1 suppressed both HBV RNA and protein expression, as well as DNA replication of both wildtype and 3TC-resistant virus. Time-course analyses revealed that RNA expression was blocked first after treatment with 8-1, followed by viral proteins, and then DNA. 8-1 inhibited the activity of all HBV promoters by decreasing the binding of hepatocyte nuclear factor 4 (HNF-4), HNF-3, and fetoprotein factor to the precore/core promoter enhancer II region. The amount of HNF-4 and HNF-3 was decreased posttranscriptionally by 8-1 in HBV-producing cells, but not in HBV-negative cells. Therefore, 8-1 suppresses HBV replication by posttranscriptional down-regulation of critical transcription factors in HBV-producing cells, thus diminishing HBV promoter activity and blocking viral gene expression and replication. This mechanism is unique and different from other anti-HBV compounds previously described. © 2007 by The National Academy of Sciences of the USA.en_US
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.meshAntiviral Agents - Chemistry - Pharmacologyen_US
dc.subject.meshBenzodioxoles - Chemistry - Pharmacologyen_US
dc.subject.meshCell Death - Drug Effectsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshDna, Viral - Metabolismen_US
dc.subject.meshDown-Regulation - Drug Effectsen_US
dc.subject.meshHepatitis B Virus - Drug Effects - Geneticsen_US
dc.subject.meshHepatocyte Nuclear Factors - Genetics - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshLamivudine - Pharmacologyen_US
dc.subject.meshLignansen_US
dc.subject.meshModels, Biologicalen_US
dc.subject.meshPhthalazines - Chemistry - Pharmacologyen_US
dc.subject.meshPromoter Regions, Genetic - Geneticsen_US
dc.subject.meshProtein Binding - Drug Effectsen_US
dc.subject.meshRna Stability - Drug Effectsen_US
dc.subject.meshRna, Viral - Metabolismen_US
dc.subject.meshThermodynamicsen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshTranscription, Genetic - Drug Effectsen_US
dc.subject.meshViral Proteins - Metabolismen_US
dc.subject.meshXanthines - Chemistry - Pharmacologyen_US
dc.titleUnique antiviral mechanism discovered in anti-hepatitis B virus research with a natural product analogueen_US
dc.typeArticleen_US
dc.identifier.emailLeung, CH:duncanl@hkucc.hku.hken_US
dc.identifier.authorityLeung, CH=rp00730en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1073/pnas.0609883104en_US
dc.identifier.pmid17488817-
dc.identifier.scopuseid_2-s2.0-34347223650en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34347223650&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume104en_US
dc.identifier.issue20en_US
dc.identifier.spage8526en_US
dc.identifier.epage8531en_US
dc.identifier.isiWOS:000246599900060-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYing, C=7101886519en_US
dc.identifier.scopusauthoridLi, Y=26642866500en_US
dc.identifier.scopusauthoridLeung, CH=7402612570en_US
dc.identifier.scopusauthoridRobek, MD=6507620977en_US
dc.identifier.scopusauthoridCheng, YC=36041844200en_US
dc.identifier.citeulike2192598-

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