{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T02:15:14Z","timestamp":1779329714185,"version":"3.51.4"},"reference-count":27,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81525018"],"award-info":[{"award-number":["81525018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Bureau of Beijing Municipal Government"},{"name":"Beijing Municipal Commission of Science and Technology","award":["D171100003117003"],"award-info":[{"award-number":["D171100003117003"]}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Research"],"published-print":{"date-parts":[[2019,8]]},"DOI":"10.1016\/j.antiviral.2019.06.002","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T15:05:16Z","timestamp":1559747116000},"page":"197-202","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"special_numbering":"C","title":["A quantitative method for hepatitis B virus covalently closed circular DNA enables distinguishing direct acting antivirals from cytotoxic agents"],"prefix":"10.1016","volume":"168","author":[{"given":"Zhenchao","family":"Gao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liwei","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhui","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.antiviral.2019.06.002_bib1","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00560-17","article-title":"Capsid assembly modulators have a dual mechanism of action in primary human hepatocytes infected with hepatitis B virus","volume":"61","author":"Berke","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.antiviral.2019.06.002_bib2","first-page":"41","article-title":"Quantification of HBV covalently closed circular DNA from liver tissue by real-time PCR","volume":"95","author":"Bowden","year":"2004","journal-title":"Methods Mol. Med."},{"key":"10.1016\/j.antiviral.2019.06.002_bib3","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0165-4608(93)90227-D","article-title":"Cytogenetic studies on human liver cancer cell lines","volume":"65","author":"Chen","year":"1993","journal-title":"Cancer Genet. Cytogenet."},{"key":"10.1016\/j.antiviral.2019.06.002_bib4","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1128\/AAC.00138-06","article-title":"Intracellular metabolism and in vitro activity of tenofovir against hepatitis B virus","volume":"50","author":"Delaney","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.antiviral.2019.06.002_bib5","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/j.jhep.2016.02.016","article-title":"New antiviral targets for innovative treatment concepts for hepatitis B virus and hepatitis delta virus","volume":"64","author":"Durantel","year":"2016","journal-title":"J. Hepatol."},{"key":"10.1016\/j.antiviral.2019.06.002_bib6","doi-asserted-by":"crossref","first-page":"6164","DOI":"10.1128\/JVI.02721-06","article-title":"Formation of hepatitis B virus covalently closed circular DNA: removal of genome-linked protein","volume":"81","author":"Gao","year":"2007","journal-title":"J. Virol."},{"key":"10.1016\/j.antiviral.2019.06.002_bib7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1006658","article-title":"HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways","volume":"13","author":"Guo","year":"2017","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.antiviral.2019.06.002_bib8","doi-asserted-by":"crossref","first-page":"12472","DOI":"10.1128\/JVI.01123-07","article-title":"Characterization of the intracellular deproteinized relaxed circular DNA of hepatitis B virus: an intermediate of covalently closed circular DNA formation","volume":"81","author":"Guo","year":"2007","journal-title":"J. Virol."},{"key":"10.1016\/j.antiviral.2019.06.002_bib9","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.antiviral.2015.08.005","article-title":"Metabolism and function of hepatitis B virus cccDNA: implications for the development of cccDNA-targeting antiviral therapeutics","volume":"122","author":"Guo","year":"2015","journal-title":"Antivir. Res."},{"key":"10.1016\/j.antiviral.2019.06.002_bib10","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/0022-2836(67)90307-5","article-title":"Selective extraction of polyoma DNA from infected mouse cell cultures","volume":"26","author":"Hirt","year":"1967","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.antiviral.2019.06.002_bib11","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.jhep.2018.08.012","article-title":"Hepatitis B virus genome recycling and de novo secondary infection events maintain stable cccDNA levels","volume":"69","author":"Ko","year":"2018","journal-title":"J. Hepatol."},{"key":"10.1016\/j.antiviral.2019.06.002_bib12","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1006784","article-title":"The role of host DNA ligases in hepadnavirus covalently closed circular DNA formation","volume":"13","author":"Long","year":"2017","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.antiviral.2019.06.002_bib13","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.mad.2016.12.005","article-title":"Mitochondrial activity and dynamics changes regarding metabolism in ageing and obesity","volume":"162","author":"Lopez-Lluch","year":"2017","journal-title":"Mech. Ageing Dev."},{"key":"10.1016\/j.antiviral.2019.06.002_bib14","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00539-17","article-title":"Identification of an intermediate in hepatitis B virus covalently closed circular (CCC) DNA formation and sensitive and selective CCC DNA detection","volume":"91","author":"Luo","year":"2017","journal-title":"J. Virol."},{"key":"10.1016\/j.antiviral.2019.06.002_bib15","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1002\/hep.510270638","article-title":"Molecular basis for persistent hepatitis B virus infection in the liver after clearance of serum hepatitis B surface antigen","volume":"27","author":"Mason","year":"1998","journal-title":"Hepatology"},{"key":"10.1016\/j.antiviral.2019.06.002_bib16","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/0042-6822(84)90231-9","article-title":"Hepatitis B virus DNA forms in nuclear and cytoplasmic fractions of infected human liver","volume":"137","author":"Miller","year":"1984","journal-title":"Virology"},{"key":"10.1016\/j.antiviral.2019.06.002_bib17","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1136\/gutjnl-2015-309809","article-title":"HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B","volume":"64","author":"Nassal","year":"2015","journal-title":"Gut"},{"key":"10.1016\/j.antiviral.2019.06.002_bib18","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1128\/JVI.69.6.3350-3357.1995","article-title":"The covalently closed duplex form of the hepadnavirus genome exists in situ as a heterogeneous population of viral minichromosomes","volume":"69","author":"Newbold","year":"1995","journal-title":"J. Virol."},{"key":"10.1016\/j.antiviral.2019.06.002_bib19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005893","article-title":"DNA polymerase kappa is a key cellular factor for the formation of covalently closed circular DNA of hepatitis B virus","volume":"12","author":"Qi","year":"2016","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.antiviral.2019.06.002_bib20","doi-asserted-by":"crossref","DOI":"10.21769\/BioProtoc.3202","article-title":"Quantification of hepatitis B virus covalently closed circular DNA in infected cell culture models by quantitative PCR","volume":"9","author":"Qu","year":"2019","journal-title":"Bio-protocol"},{"issue":"7","key":"10.1016\/j.antiviral.2019.06.002_bib21","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S2468-1253(19)30119-0","article-title":"A global scientific strategy to cure hepatitis B","volume":"4","author":"Revill","year":"2019","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"10.1016\/j.antiviral.2019.06.002_bib22","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.virol.2015.02.031","article-title":"Molecular biology of hepatitis B virus infection","volume":"479\u2013480","author":"Seeger","year":"2015","journal-title":"Virology"},{"key":"10.1016\/j.antiviral.2019.06.002_bib23","doi-asserted-by":"crossref","first-page":"e216","DOI":"10.1038\/mtna.2014.68","article-title":"Targeting hepatitis B virus with CRISPR\/Cas9","volume":"3","author":"Seeger","year":"2014","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10.1016\/j.antiviral.2019.06.002_bib24","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/hep4.1281","article-title":"Hepatitis B treatment: what we know now and what remains to Be researched","volume":"3","author":"Suk-Fong Lok","year":"2019","journal-title":"Hepatol. Commun."},{"key":"10.1016\/j.antiviral.2019.06.002_bib25","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/0092-8674(86)90602-1","article-title":"Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells","volume":"47","author":"Tuttleman","year":"1986","journal-title":"Cell"},{"key":"10.1016\/j.antiviral.2019.06.002_bib26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/978-1-4939-6700-1_6","article-title":"Analyses of HBV cccDNA quantification and modification","volume":"1540","author":"Xia","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.antiviral.2019.06.002_bib27","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.antiviral.2006.05.006","article-title":"Hepatitis B virus e antigen production is dependent upon covalently closed circular (ccc) DNA in HepAD38 cell cultures and may serve as a cccDNA surrogate in antiviral screening assays","volume":"72","author":"Zhou","year":"2006","journal-title":"Antivir. Res."}],"container-title":["Antiviral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0166354219302426?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0166354219302426?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T05:49:38Z","timestamp":1608184178000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0166354219302426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8]]},"references-count":27,"alternative-id":["S0166354219302426"],"URL":"https:\/\/doi.org\/10.1016\/j.antiviral.2019.06.002","relation":{},"ISSN":["0166-3542"],"issn-type":[{"value":"0166-3542","type":"print"}],"subject":[],"published":{"date-parts":[[2019,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A quantitative method for hepatitis B virus covalently closed circular DNA enables distinguishing direct acting antivirals from cytotoxic agents","name":"articletitle","label":"Article Title"},{"value":"Antiviral Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.antiviral.2019.06.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}