{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T19:49:02Z","timestamp":1782935342549,"version":"3.54.5"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25fk0310534"],"award-info":[{"award-number":["JP25fk0310534"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25fk0310534"],"award-info":[{"award-number":["JP25fk0310534"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25fk0310534"],"award-info":[{"award-number":["JP25fk0310534"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25fk0310534"],"award-info":[{"award-number":["JP25fk0310534"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP223fa627006"],"award-info":[{"award-number":["JP223fa627006"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP223fa627006"],"award-info":[{"award-number":["JP223fa627006"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP223fa627006"],"award-info":[{"award-number":["JP223fa627006"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gilead Sciences, Inc.","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Gilead Sciences, Inc.","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Gilead Sciences, Inc.","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"GSK plc.","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Bristol Myers Squibb","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Basis for Supporting Innovative Drug Discovery and Life Science Research","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background and aim<\/jats:title>\n                    <jats:p>Hepatitis B surface antigen (HBsAg) is associated with hepatocellular carcinoma risk and immune exhaustion and contributes to hepatitis B virus (HBV) persistence. Current anti-HBV treatments have a limited ability to reduce HBsAg levels. This study aimed to identify FDA-approved drugs capable of reducing HBsAg levels and explore the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 1134 FDA-approved compounds were screened at 9.9 \u03bcM for 7 days using HepG2.2.15.7 cells, which contain an integrated HBV genome. HBsAg in the supernatant and cell viability were assessed. Compounds whose viability was reduced by &gt;1 SD were excluded. Compounds whose HBsAg concentration decreased by &gt;1.5 SD were selected and validated at 0.5 and 5 \u03bcM. We evaluated the HBsAg-reducing effect of the final candidate compounds using HBV-infected primary human hepatocytes (HepaSH cells) derived from chimeric TK-NOG mice and investigated the underlying mechanism responsible for the reduction in HBsAg.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After 126 cytotoxic compounds were excluded, the HBsAg levels of the 6 candidates decreased by &gt;1.5 SD. Ethacridine and auranofin significantly reduced the level of HBsAg at both 5 and 0.5 \u03bcM. In HepaSH cells, only auranofin decreased the level of HBsAg. Auranofin did not affect the HBe antigen, HBV-DNA, or pregenomic RNA, nor did it reduce the level of intracellular HBsAg, as determined by Western blotting. Transmission electron microscopy revealed more vesicles in auranofin-treated HepaSH cells than in control cells. Immunofluorescence analysis of HepaSH cells treated with auranofin revealed increased Galectin-3 expression and colocalization of HBsAg with Galectin-3, which was consistent with lysosomal damage, compared with those of the untreated controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Auranofin, an FDA-approved antirheumatic agent, reduces HBsAg secretion via lysosomal damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0340023","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T18:35:30Z","timestamp":1768588530000},"page":"e0340023","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Auranofin, identified by FDA-approved drug library screening, inhibits HBs antigen secretion via lysosomal damage"],"prefix":"10.1371","volume":"21","author":[{"given":"Akiyoshi","family":"Shimoda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8634-2922","authenticated-orcid":true,"given":"Kazuhiro","family":"Murai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2488-7315","authenticated-orcid":true,"given":"Hayato","family":"Hikita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5043-3435","authenticated-orcid":true,"given":"Satoshi","family":"Minami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Miyake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kuriki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Sometani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihyun","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Shigeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Higuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Maesaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Shirai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9116-7054","authenticated-orcid":true,"given":"Yuki","family":"Tahata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Kodama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Suemizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Takehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"pone.0340023.ref001","unstructured":"World Health Organization. Fact Sheet, Hepatits B. 2024. [cited 15 January 2025]. Available from: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-b"},{"issue":"4","key":"pone.0340023.ref002","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance","volume":"67","author":"NA Terrault","year":"2018","journal-title":"Hepatology"},{"issue":"2","key":"pone.0340023.ref003","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection","volume":"67","author":"European Association for the Study of the Liver","year":"2017","journal-title":"J Hepatol"},{"key":"pone.0340023.ref004","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1111\/hepr.13504","article-title":"Japan society of hepatology guidelines for the management of hepatitis b virus infection: 2019 update","volume":"50","author":"Drafting Committee for Hepatitis Management Guidelines","year":"2020","journal-title":"Hepatol Res"},{"issue":"1","key":"pone.0340023.ref005","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1159\/000082092","article-title":"Hepatitis B virus-related hepatocellular carcinogenesis and its prevention","volume":"48","author":"K Ikeda","year":"2005","journal-title":"Intervirology"},{"issue":"1","key":"pone.0340023.ref006","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/jmv.10559","article-title":"Hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in chronic carriers","volume":"72","author":"B Tang","year":"2004","journal-title":"J Med Virol"},{"issue":"4","key":"pone.0340023.ref007","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/jnci\/dji043","article-title":"Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a prospective study in men","volume":"97","author":"M-W Yu","year":"2005","journal-title":"J Natl Cancer Inst"},{"issue":"9","key":"pone.0340023.ref008","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1111\/hepr.14225","article-title":"The Risk of Developing Hepatocellular Carcinoma Persists in Chronic Hepatitis B Patients Even After the Long-Term Administration of Nucleos(t)ide Analogs","volume":"55","author":"K Murai","year":"2025","journal-title":"Hepatol Res"},{"key":"pone.0340023.ref009","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/hepr.14111","article-title":"High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs","volume":"55","author":"E Sometani","year":"2024","journal-title":"Hepatol Res"},{"issue":"5","key":"pone.0340023.ref010","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1053\/j.gastro.2012.02.007","article-title":"High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load","volume":"142","author":"T-C Tseng","year":"2012","journal-title":"Gastroenterology"},{"issue":"4","key":"pone.0340023.ref011","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.jhep.2009.10.033","article-title":"Mechanisms of HBV-related hepatocarcinogenesis","volume":"52","author":"C Neuveut","year":"2010","journal-title":"J Hepatol"},{"issue":"1","key":"pone.0340023.ref012","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1053\/j.gastro.2014.04.030","article-title":"Strategies to inhibit entry of HBV and HDV into hepatocytes","volume":"147","author":"S Urban","year":"2014","journal-title":"Gastroenterology"},{"issue":"6","key":"pone.0340023.ref013","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/0092-8674(89)90770-8","article-title":"Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice","volume":"59","author":"FV Chisari","year":"1989","journal-title":"Cell"},{"issue":"3","key":"pone.0340023.ref014","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3390\/v9030056","article-title":"Complete and Incomplete Hepatitis B Virus Particles: Formation, Function, and Application","volume":"9","author":"J Hu","year":"2017","journal-title":"Viruses"},{"key":"pone.0340023.ref015","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.virol.2017.05.017","article-title":"Hepatitis B surface antigen on subviral particles reduces the neutralizing effect of anti-HBs antibodies on hepatitis B viral particles in vitro","volume":"509","author":"GE Rydell","year":"2017","journal-title":"Virology"},{"issue":"2","key":"pone.0340023.ref016","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.jhep.2020.04.013","article-title":"Hepatitis B surface antigen seroclearance: Immune mechanisms, clinical impact, importance for drug development","volume":"73","author":"I Tout","year":"2020","journal-title":"J Hepatol"},{"issue":"21","key":"pone.0340023.ref017","doi-asserted-by":"crossref","first-page":"8623","DOI":"10.1073\/pnas.0809818106","article-title":"High antigen levels are the cause of T cell exhaustion during chronic viral infection","volume":"106","author":"SN Mueller","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7077","key":"pone.0340023.ref018","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nature04444","article-title":"Restoring function in exhausted CD8 T cells during chronic viral infection","volume":"439","author":"DL Barber","year":"2006","journal-title":"Nature"},{"key":"pone.0340023.ref019","first-page":"935295","article-title":"Hepatitis B surface antigen could contribute to the immunopathogenesis of hepatitis B virus infection","volume":"2013","author":"Y Kondo","year":"2013","journal-title":"ISRN Gastroenterol"},{"key":"pone.0340023.ref020","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/liv.12749","article-title":"HBV and the immune response","author":"C Ferrari","year":"2015","journal-title":"Liver Int"},{"issue":"3","key":"pone.0340023.ref021","article-title":"T-cell exhaustion in chronic hepatitis B infection: current knowledge and clinical significance","volume":"6","author":"B Ye","year":"2015","journal-title":"Cell Death Dis"},{"issue":"4","key":"pone.0340023.ref022","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1002\/hep.29323","article-title":"Hepatitis B cure: From discovery to regulatory approval","volume":"66","author":"AS Lok","year":"2017","journal-title":"Hepatology"},{"issue":"10","key":"pone.0340023.ref023","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1016\/j.drudis.2019.06.014","article-title":"Drug repurposing: a promising tool to accelerate the drug discovery process","volume":"24","author":"V Parvathaneni","year":"2019","journal-title":"Drug Discov Today"},{"issue":"3","key":"pone.0340023.ref024","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.bbrc.2014.08.029","article-title":"Formation of covalently closed circular DNA in Hep38.7-Tet cells, a tetracycline inducible hepatitis B virus expression cell line","volume":"452","author":"N Ogura","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"issue":"11","key":"pone.0340023.ref025","doi-asserted-by":"crossref","first-page":"6759","DOI":"10.3390\/md13116759","article-title":"Identification of Antiviral Agents Targeting Hepatitis B Virus Promoter from Extracts of Indonesian Marine Organisms by a Novel Cell-Based Screening Assay","volume":"13","author":"A Yamashita","year":"2015","journal-title":"Mar Drugs"},{"key":"pone.0340023.ref026","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbrc.2023.04.054","article-title":"HepaSH cells: Experimental human hepatocytes with lesser inter-individual variation and more sustainable availability than primary human hepatocytes","volume":"663","author":"S Uehara","year":"2023","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"pone.0340023.ref027","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.bbrc.2020.04.031","article-title":"SIRT1 enhances hepatitis virus B transcription independent of hepatic autophagy","volume":"527","author":"T Yamai","year":"2020","journal-title":"Biochem Biophys Res Commun"},{"issue":"11","key":"pone.0340023.ref028","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.3390\/v14112468","article-title":"Ivermectin Inhibits HBV Entry into the Nucleus by Suppressing KPNA2","volume":"14","author":"A Nakanishi","year":"2022","journal-title":"Viruses"},{"key":"pone.0340023.ref029","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1099\/vir.0.009928-0","article-title":"Stimulation of hepatitis B virus genome replication by HBx is linked to both nuclear and cytoplasmic HBx expression","volume":"90","author":"M-Y Cha","year":"2009","journal-title":"J Gen Virol"},{"issue":"23","key":"pone.0340023.ref030","doi-asserted-by":"crossref","first-page":"13689","DOI":"10.1128\/JVI.02035-14","article-title":"DDX3 DEAD-box RNA helicase is a host factor that restricts hepatitis B virus replication at the transcriptional level","volume":"88","author":"C Ko","year":"2014","journal-title":"J Virol"},{"key":"pone.0340023.ref031","doi-asserted-by":"crossref","first-page":"589040","DOI":"10.3389\/fmed.2020.589040","article-title":"Hepatocyte Endoplasmic Reticulum Stress Inhibits Hepatitis B Virus Secretion and Delays Intracellular Hepatitis B Virus Clearance After Entecavir Treatment","volume":"7","author":"H Chen","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"pone.0340023.ref032","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.freeradbiomed.2017.05.005","article-title":"Differential redox sensitivity of cathepsin B and L holds the key to autophagy-apoptosis interplay after Thioredoxin reductase inhibition in nutritionally stressed SH-SY5Y cells","volume":"108","author":"P Nagakannan","year":"2017","journal-title":"Free Radic Biol Med"},{"issue":"4","key":"pone.0340023.ref033","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s13402-021-00603-2","article-title":"Identification of lysosome-targeting drugs with anti-inflammatory activity as potential invasion inhibitors of treatment resistant HER2 positive cancers","volume":"44","author":"MB Hansen","year":"2021","journal-title":"Cell Oncol (Dordr)"},{"issue":"8","key":"pone.0340023.ref034","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1080\/15548627.2015.1063871","article-title":"Sensitive detection of lysosomal membrane permeabilization by lysosomal galectin puncta assay","volume":"11","author":"S Aits","year":"2015","journal-title":"Autophagy"},{"issue":"21","key":"pone.0340023.ref035","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1056\/NEJMoa2210027","article-title":"Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection","volume":"387","author":"M-F Yuen","year":"2022","journal-title":"N Engl J Med"},{"key":"pone.0340023.ref036","doi-asserted-by":"crossref","first-page":"215323","DOI":"10.1016\/j.ccr.2023.215323","article-title":"Molecular mechanisms and clinical implications of the gold drug auranofin","volume":"493","author":"S Shen","year":"2023","journal-title":"Coord Chem Rev"},{"issue":"5","key":"pone.0340023.ref037","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1182\/blood.V62.5.1070.1070","article-title":"The mechanism of action of the antiinflammatory agents dexamethasone and Auranofin in human polymorphonuclear leukocytes","volume":"62","author":"TD Coates","year":"1983","journal-title":"Blood"},{"issue":"3","key":"pone.0340023.ref038","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1007\/s12272-001-1166-9","article-title":"Auranofin, an immunosuppressive drug, inhibits MHC class I and MHC class II pathways of antigen presentation in dendritic cells","volume":"31","author":"S Han","year":"2008","journal-title":"Arch Pharm Res"},{"key":"pone.0340023.ref039","first-page":"4844","article-title":"ET-18-OCH3 Inhibits Nuclear Factor-\u03baB Activation by 12-O-Tetradecanoylphorbol-13-acetate but not by Tumor Necrosis Factor-\u03b1 or Interleukin 1\u03b11","volume":"55","author":"L Daniel","year":"1995","journal-title":"Cancer Research"},{"issue":"4","key":"pone.0340023.ref040","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1111\/j.1365-2567.2007.02679.x","article-title":"Auranofin blocks interleukin-6 signalling by inhibiting phosphorylation of JAK1 and STAT3","volume":"122","author":"N-H Kim","year":"2007","journal-title":"Immunology"},{"issue":"14","key":"pone.0340023.ref041","doi-asserted-by":"crossref","first-page":"5453","DOI":"10.18632\/oncotarget.2113","article-title":"Clinically used antirheumatic agent auranofin is a proteasomal deubiquitinase inhibitor and inhibits tumor growth","volume":"5","author":"N Liu","year":"2014","journal-title":"Oncotarget"},{"issue":"19","key":"pone.0340023.ref042","doi-asserted-by":"crossref","first-page":"9118","DOI":"10.18632\/oncotarget.2361","article-title":"Anti-rheumatic agent auranofin induced apoptosis in chronic myeloid leukemia cells resistant to imatinib through both Bcr\/Abl-dependent and -independent mechanisms","volume":"5","author":"X Chen","year":"2014","journal-title":"Oncotarget"},{"issue":"9","key":"pone.0340023.ref043","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1158\/0008-5472.CAN-13-2033","article-title":"Auranofin induces lethal oxidative and endoplasmic reticulum stress and exerts potent preclinical activity against chronic lymphocytic leukemia","volume":"74","author":"W Fiskus","year":"2014","journal-title":"Cancer Res"},{"issue":"4","key":"pone.0340023.ref044","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1002\/hep.30467","article-title":"Induction of Oxidative Stress Through Inhibition of Thioredoxin Reductase 1 Is an Effective Therapeutic Approach for Hepatocellular Carcinoma","volume":"69","author":"D Lee","year":"2019","journal-title":"Hepatology"},{"issue":"12","key":"pone.0340023.ref045","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2013.473","article-title":"A candidate anti-HIV reservoir compound, auranofin, exerts a selective \u201canti-memory\u201d effect by exploiting the baseline oxidative status of lymphocytes","volume":"4","author":"B Chirullo","year":"2013","journal-title":"Cell Death Dis"},{"key":"pone.0340023.ref046","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.antiviral.2017.04.014","article-title":"Host oxidative folding pathways offer novel anti-chikungunya virus drug targets with broad spectrum potential","volume":"143","author":"RM Langsjoen","year":"2017","journal-title":"Antiviral Res"},{"key":"pone.0340023.ref047","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.virol.2020.05.002","article-title":"The FDA-approved gold drug auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells","volume":"547","author":"HA Rothan","year":"2020","journal-title":"Virology"},{"key":"pone.0340023.ref048","doi-asserted-by":"crossref","first-page":"9247574","DOI":"10.1155\/2017\/9247574","article-title":"The Many Roles of Galectin-3, a Multifaceted Molecule, in Innate Immune Responses against Pathogens","volume":"2017","author":"L D\u00edaz-Alvarez","year":"2017","journal-title":"Mediators Inflamm"},{"issue":"1","key":"pone.0340023.ref049","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.devcel.2019.10.025","article-title":"Galectin-3 Coordinates a Cellular System for Lysosomal Repair and Removal","volume":"52","author":"J Jia","year":"2020","journal-title":"Dev Cell"},{"issue":"12","key":"pone.0340023.ref050","doi-asserted-by":"crossref","first-page":"4427","DOI":"10.1128\/AAC.00541-07","article-title":"A substituted tetrahydro-tetrazolo-pyrimidine is a specific and novel inhibitor of hepatitis B virus surface antigen secretion","volume":"51","author":"AM Dougherty","year":"2007","journal-title":"Antimicrob Agents Chemother"},{"key":"pone.0340023.ref051","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.ebiom.2019.10.022","article-title":"Niacin analogue, 6-Aminonicotinamide, a novel inhibitor of hepatitis B virus replication and HBsAg production","volume":"49","author":"F Ren","year":"2019","journal-title":"EBioMedicine"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0340023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T18:35:44Z","timestamp":1768588544000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0340023"}},"subtitle":[],"editor":[{"given":"Tatsuo","family":"Kanda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0340023","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]}}}