{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:13:03Z","timestamp":1793059983701,"version":"4.5.0"},"reference-count":45,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T00:00:00Z","timestamp":1700265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012217","name":"Xuzhou Medical University","doi-asserted-by":"publisher","award":["D2021007"],"award-info":[{"award-number":["D2021007"]}],"id":[{"id":"10.13039\/501100012217","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012217","name":"Xuzhou Medical University","doi-asserted-by":"publisher","award":["D2021008"],"award-info":[{"award-number":["D2021008"]}],"id":[{"id":"10.13039\/501100012217","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32100117"],"award-info":[{"award-number":["32100117"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32100118"],"award-info":[{"award-number":["32100118"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270161"],"award-info":[{"award-number":["32270161"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Virologica Sinica"],"published-print":{"date-parts":[[2024,2]]},"DOI":"10.1016\/j.virs.2023.11.006","type":"journal-article","created":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T17:36:41Z","timestamp":1700415401000},"page":"123-133","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"title":["Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions"],"prefix":"10.1016","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9241-1414","authenticated-orcid":false,"given":"Hongbo","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiudi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique M.A.","family":"Verstegen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jikai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renxian","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiucheng","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuiyang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc J.W.","family":"van der Laan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9982-6184","authenticated-orcid":false,"given":"Qiuwei","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7330-262X","authenticated-orcid":false,"given":"Wenshi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.virs.2023.11.006_bib1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrrheum.2010.214","article-title":"Hepatotoxicity related to antirheumatic drugs","volume":"7","author":"Aithal","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"10.1016\/j.virs.2023.11.006_bib2","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/bph.13798","article-title":"Drug repurposing from the perspective of pharmaceutical companies","volume":"175","author":"Cha","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.virs.2023.11.006_bib3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.antiviral.2019.04.005","article-title":"Suppression of pyrimidine biosynthesis by targeting DHODH enzyme robustly inhibits rotavirus replication","volume":"167","author":"Chen","year":"2019","journal-title":"Antivir. Res."},{"key":"10.1016\/j.virs.2023.11.006_bib4","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1053\/j.gastro.2014.08.040","article-title":"A\u00a0mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients","volume":"147","author":"Debing","year":"2014","journal-title":"Gastroenterology"},{"key":"10.1016\/j.virs.2023.11.006_bib5","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.jhep.2016.05.002","article-title":"Hepatitis E virus mutations associated with ribavirin treatment failure result in altered viral fitness and ribavirin sensitivity","volume":"65","author":"Debing","year":"2016","journal-title":"J.\u00a0Hepatol."},{"key":"10.1016\/j.virs.2023.11.006_bib6","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/tid.12353","article-title":"Successful treatment of hepatitis E virus-associated cryoglobulinemic membranoproliferative glomerulonephritis with ribavirin","volume":"17","author":"Del Bello","year":"2015","journal-title":"Transpl. Infect. Dis."},{"key":"10.1016\/j.virs.2023.11.006_bib7","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.3201\/eid2805.212546","article-title":"Viral hepatitis E outbreaks in refugees and internally displaced populations, sub-Saharan Africa, 2010-2020","volume":"28","author":"Desai","year":"2022","journal-title":"Emerg. Infect. Dis."},{"key":"10.1016\/j.virs.2023.11.006_bib8","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s40265-020-01464-z","article-title":"Lonafarnib: first approval","volume":"81","author":"Dhillon","year":"2021","journal-title":"Drugs"},{"key":"10.1016\/j.virs.2023.11.006_bib9","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1016\/S0140-6736(22)00454-8","article-title":"Host-targeting oral antiviral drugs to prevent pandemics","volume":"399","author":"Dwek","year":"2022","journal-title":"Lancet"},{"key":"10.1016\/j.virs.2023.11.006_bib11","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/acn3.51574","article-title":"A\u00a0double-blind, randomized, placebo-controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing-remitting multiple sclerosis","volume":"9","author":"Fox","year":"2022","journal-title":"Ann Clin Transl Neurol"},{"key":"10.1016\/j.virs.2023.11.006_bib12","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1053\/j.ajkd.2015.10.022","article-title":"Hepatitis E virus-Induced cryoglobulinemic glomerulonephritis in a nonimmunocompromised person","volume":"67","author":"Guinault","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"10.1016\/j.virs.2023.11.006_bib13","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.3390\/v14081778","article-title":"Inhibition of hepatitis E virus replication by novel inhibitor targeting methyltransferase","volume":"14","author":"Hooda","year":"2022","journal-title":"Viruses"},{"key":"10.1016\/j.virs.2023.11.006_bib14","doi-asserted-by":"crossref","first-page":"W739","DOI":"10.1093\/nar\/gkac382","article-title":"SynergyFinder 3.0: an interactive analysis and consensus interpretation of multi-drug synergies across multiple samples","volume":"50","author":"Ianevski","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.virs.2023.11.006_bib15","doi-asserted-by":"crossref","first-page":"105096","DOI":"10.1016\/j.tiv.2021.105096","article-title":"Investigating dihydroorotate dehydrogenase inhibitor mediated mitochondrial dysfunction in hepatic in vitro models","volume":"72","author":"Jones","year":"2021","journal-title":"Toxicol. Vitro"},{"key":"10.1016\/j.virs.2023.11.006_bib16","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.clinre.2014.07.005","article-title":"Hepatitis E virus: chronic infection, extra-hepatic manifestations, and treatment","volume":"39","author":"Kamar","year":"2015","journal-title":"Clin Res Hepatol Gastroenterol"},{"key":"10.1016\/j.virs.2023.11.006_bib17","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.3390\/v14102116","article-title":"Unmet needs for the treatment of chronic hepatitis E virus infection in Immunocompromised patients","volume":"14","author":"Kamar","year":"2022","journal-title":"Viruses"},{"key":"10.1016\/j.virs.2023.11.006_bib18","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1056\/NEJMoa1215246","article-title":"Ribavirin for chronic hepatitis E virus infection in transplant recipients","volume":"370","author":"Kamar","year":"2014","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.virs.2023.11.006_bib19","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/liv.13037","article-title":"Extrahepatic manifestations of hepatitis E virus","volume":"36","author":"Kamar","year":"2016","journal-title":"Liver Int."},{"key":"10.1016\/j.virs.2023.11.006_bib20","first-page":"345","article-title":"Massive hemolysis causing renal failure in acute hepatitis E infection","volume":"4","author":"Karki","year":"2016","journal-title":"J\u00a0Clin Transl Hepatol"},{"key":"10.1016\/j.virs.2023.11.006_bib21","doi-asserted-by":"crossref","first-page":"e00754-17","DOI":"10.1128\/JVI.00754-17","article-title":"Zinc salts block hepatitis E virus replication by inhibiting the activity of viral RNA-dependent RNA polymerase","volume":"91","author":"Kaushik","year":"2017","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.virs.2023.11.006_bib22","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3390\/v11060485","article-title":"Hepatitis E Virus Drug Development","volume":"11","author":"Kinast","year":"2019","journal-title":"Viruses"},{"key":"10.1016\/j.virs.2023.11.006_bib23","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1002\/hep.26686","article-title":"No detectable resistance to tenofovir disoproxil fumarate after 6 years of therapy in patients with chronic hepatitis B","volume":"59","author":"Kitrinos","year":"2014","journal-title":"Hepatology"},{"key":"10.1016\/j.virs.2023.11.006_bib24","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1111\/liv.14468","article-title":"The global epidemiology of hepatitis E virus infection: a systematic review and meta-analysis","volume":"40","author":"Li","year":"2020","journal-title":"Liver Int."},{"key":"10.1016\/j.virs.2023.11.006_bib25","article-title":"Recapitulating hepatitis E virus-host interactions and facilitating antiviral drug discovery in human liver-derived organoids","volume":"8","author":"Li","year":"2022","journal-title":"Sci. Adv."},{"key":"10.1016\/j.virs.2023.11.006_bib26","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.antiviral.2018.08.012","article-title":"Inhibiting pyrimidine biosynthesis impairs Ebola virus replication through depletion of nucleoside pools and activation of innate immune responses","volume":"158","author":"Luthra","year":"2018","journal-title":"Antivir. Res."},{"key":"10.1016\/j.virs.2023.11.006_bib27","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/ppul.1950010603","article-title":"Ribavirin and RSV: a new approach to an old disease","volume":"1","author":"Mcbride","year":"1985","journal-title":"Pediatr. Pulmonol."},{"key":"10.1016\/j.virs.2023.11.006_bib28","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s13318-020-00623-7","article-title":"Safety, tolerability and pharmacokinetics of vidofludimus calcium (IMU-838) after single and multiple Ascending oral doses in healthy male Subjects","volume":"45","author":"Muehler","year":"2020","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"10.1016\/j.virs.2023.11.006_bib29","doi-asserted-by":"crossref","first-page":"102129","DOI":"10.1016\/j.msard.2020.102129","article-title":"Vidofludimus calcium, a next generation DHODH inhibitor for the Treatment of relapsing-remitting multiple sclerosis","volume":"43","author":"Muehler","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"10.1016\/j.virs.2023.11.006_bib30","doi-asserted-by":"crossref","first-page":"e00003","DOI":"10.1128\/AAC.00003-19","article-title":"Antiviral candidates for treating hepatitis e virus infection","volume":"63","author":"Netzler","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"10.1016\/j.virs.2023.11.006_bib31","doi-asserted-by":"crossref","first-page":"15512","DOI":"10.1038\/s41598-022-19818-w","article-title":"In silico study on the Hepatitis E virus RNA Helicase and its inhibition by silvestrol, rocaglamide and other flavagline compounds","volume":"12","author":"Pedroni","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.virs.2023.11.006_bib32","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.jhep.2016.11.016","article-title":"Hepatitis E virus: infection beyond the liver?","volume":"66","author":"Pischke","year":"2017","journal-title":"J.\u00a0Hepatol."},{"key":"10.1016\/j.virs.2023.11.006_bib33","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1007\/s00705-017-3444-8","article-title":"Nucleoside analogue 2'-C-methylcytidine inhibits hepatitis E virus replication but antagonizes ribavirin","volume":"162","author":"Qu","year":"2017","journal-title":"Arch. Virol."},{"key":"10.1016\/j.virs.2023.11.006_bib34","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.tips.2021.01.003","article-title":"Drug repurposing for rare diseases","volume":"42","author":"Roessler","year":"2021","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.virs.2023.11.006_bib35","doi-asserted-by":"crossref","first-page":"5697","DOI":"10.1128\/JVI.00146-12","article-title":"Adaptation of a genotype 3 hepatitis E virus to efficient growth in cell culture depends on an inserted human gene segment acquired by recombination","volume":"86","author":"Shukla","year":"2012","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.virs.2023.11.006_bib36","author":"Therapeutics"},{"key":"10.1016\/j.virs.2023.11.006_bib37","unstructured":"FDA, 2010. FDA Drug Safety Communication: New boxed warning for severe liver injury with arthritis drug Arava (leflunomide). https:\/\/www.fda.gov\/drugs\/postmarket-drug-safety-information-patients-and-providers\/fda-drug-safety-communication-new-boxed-warning-severe-liver-injury-arthritis-drug-arava-leflunomide (Accessed date: 1 August 2023)."},{"key":"10.1016\/j.virs.2023.11.006_bib38","unstructured":"FDA, 2012. FDA Approved Labeling Text. www.fda.gov\/drugs. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2012\/202992s000lbl.pdfVehreschild (Accessed date: 1 August 2023)."},{"key":"10.1016\/j.virs.2023.11.006_bib39","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1007\/s40121-022-00690-0","article-title":"Safety and efficacy of vidofludimus calcium in patients hospitalized with COVID-19: a double-blind, randomized, placebo-controlled, phase 2 trial","volume":"11","author":"Vehreschild","year":"2022","journal-title":"Infect. Dis. Ther."},{"key":"10.1016\/j.virs.2023.11.006_bib40","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1111\/liv.14912","article-title":"Hepatitis E: an update on One Health and clinical medicine","volume":"41","author":"Velavan","year":"2021","journal-title":"Liver Int."},{"key":"10.1016\/j.virs.2023.11.006_bib41","doi-asserted-by":"crossref","DOI":"10.1128\/spectrum.03331-22","article-title":"Combinations of host- and virus-targeting antiviral drugs confer synergistic suppression of SARS-CoV-2","volume":"10","author":"Wagoner","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"10.1016\/j.virs.2023.11.006_bib42","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1128\/AAC.02700-15","article-title":"Cross Talk between nucleotide synthesis pathways with cellular Immunity in constraining hepatitis E virus replication","volume":"60","author":"Wang","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.virs.2023.11.006_bib43","doi-asserted-by":"crossref","first-page":"684961","DOI":"10.3389\/fonc.2021.684961","article-title":"Targeting pyrimidine metabolism in the era of precision cancer medicine","volume":"11","author":"Wang","year":"2021","journal-title":"Front. Oncol."},{"key":"10.1016\/j.virs.2023.11.006_bib44","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.03372-22","article-title":"Ribavirin treatment failure-associated mutation, Y1320H, in the RNA-dependent RNA polymerase of genotype 3 hepatitis E virus (HEV) enhances virus replication in a rabbit HEV infection model","volume":"14","author":"Wang","year":"2023","journal-title":"mBio"},{"key":"10.1016\/j.virs.2023.11.006_bib45","article-title":"Hepatitis E: an underestimated emerging threat","volume":"6","author":"Webb","year":"2019","journal-title":"Ther Adv Infect Dis"},{"key":"10.1016\/j.virs.2023.11.006_bib46","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s13238-020-00768-w","article-title":"Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2","volume":"11","author":"Xiong","year":"2020","journal-title":"Protein Cell"}],"container-title":["Virologica Sinica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1995820X23001384?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1995820X23001384?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T19:20:40Z","timestamp":1761852040000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1995820X23001384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["S1995820X23001384"],"URL":"https:\/\/doi.org\/10.1016\/j.virs.2023.11.006","relation":{},"ISSN":["1995-820X"],"issn-type":[{"value":"1995-820X","type":"print"}],"subject":[],"published":{"date-parts":[[2024,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions","name":"articletitle","label":"Article Title"},{"value":"Virologica Sinica","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.virs.2023.11.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.","name":"copyright","label":"Copyright"}]}}