{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:56:28Z","timestamp":1784249788803,"version":"3.55.0"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Laulima Government Solutions","award":["HHSN272201800013C"],"award-info":[{"award-number":["HHSN272201800013C"]}]},{"name":"Laulima Government Solutions","award":["HHSN272201800013C"],"award-info":[{"award-number":["HHSN272201800013C"]}]},{"DOI":"10.13039\/100000993","name":"Battelle Memorial Institute","doi-asserted-by":"publisher","award":["HHSN272200700016I"],"award-info":[{"award-number":["HHSN272200700016I"]}],"id":[{"id":"10.13039\/100000993","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI125626"],"award-info":[{"award-number":["AI125626"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI128556"],"award-info":[{"award-number":["AI128556"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Mammarenaviruses cause chronic infections in rodents, which are their predominant natural hosts. Human infection with some of these viruses causes high-consequence disease, posing significant issues in public health. Currently, no FDA-licensed mammarenavirus vaccines are available, and anti-mammarenavirus drugs are limited to an off-label use of ribavirin, which is only partially efficacious and associated with severe side effects. Dihydroorotate dehydrogenase (DHODH) inhibitors, which block de novo pyrimidine biosynthesis, have antiviral activity against viruses from different families, including Arenaviridae, the taxonomic home of mammarenaviruses. Here, we evaluate five novel DHODH inhibitors for their antiviral activity against mammarenaviruses. All tested DHODH inhibitors were potently active against lymphocytic choriomeningitis virus (LCMV) (half-maximal effective concentrations [EC50] in the low nanomolar range, selectivity index [SI] &gt; 1000). The tested DHODH inhibitors did not affect virion cell entry or budding, but rather interfered with viral RNA synthesis. This interference resulted in a potent interferon-independent inhibition of mammarenavirus multiplication in vitro, including the highly virulent Lassa and Jun\u00edn viruses.<\/jats:p>","DOI":"10.3390\/v12080821","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T07:31:45Z","timestamp":1596007905000},"page":"821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Novel Dihydroorotate Dehydrogenase Inhibitors with Potent Interferon-Independent Antiviral Activity against Mammarenaviruses In Vitro"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7300-0592","authenticated-orcid":false,"given":"Yu-Jin","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8048-410X","authenticated-orcid":false,"given":"Beatrice","family":"Cubitt","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1101-0920","authenticated-orcid":false,"given":"Yingyun","family":"Cai","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick (IRF-Frederick), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), B-8200 Research Plaza, Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7800-6045","authenticated-orcid":false,"given":"Jens H.","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Integrated Research Facility at Fort Detrick (IRF-Frederick), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), B-8200 Research Plaza, Fort Detrick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Vitt","sequence":"additional","affiliation":[{"name":"Immunic Therapeutics, New York City, NY 10036, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hella","family":"Kohlhof","sequence":"additional","affiliation":[{"name":"Immunic Therapeutics, New York City, NY 10036, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8171-8115","authenticated-orcid":false,"given":"Juan C.","family":"de la Torre","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,29]]},"reference":[{"key":"ref_1","first-page":"231","article-title":"Arenavirus quasispecies and their biological implications","volume":"392","author":"Martin","year":"2016","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.coviro.2019.08.002","article-title":"Lassa fever diagnostics: Past, present, and future","volume":"37","author":"Happi","year":"2019","journal-title":"Curr. Opin. Virol."},{"key":"ref_3","first-page":"865","article-title":"Emerging infectious diseases and risk to the traveler","volume":"83","author":"Freedman","year":"1999","journal-title":"Med. Clin. N. Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1086\/322620","article-title":"Viral hemorrhagic fever hazards for travelers in Africa","volume":"33","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1863-2378.2012.01469.x","article-title":"Lassa fever in West Africa: Evidence for an expanded region of endemicity","volume":"59","author":"Sogoba","year":"2012","journal-title":"Zoonoses Public Health"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Briese, T., Paweska, J.T., McMullan, L.K., Hutchison, S.K., Street, C., Palacios, G., Khristova, M.L., Weyer, J., Swanepoel, R., and Egholm, M. (2009). Genetic detection and characterization of Lujo virus, a new hemorrhagic fever-associated arenavirus from southern Africa. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000455"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.coviro.2014.02.007","article-title":"Epidemiology and pathogenesis of Bolivian hemorrhagic fever","volume":"5","author":"Patterson","year":"2014","journal-title":"Curr. Opin. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Delgado, S., Erickson, B.R., Agudo, R., Blair, P.J., Vallejo, E., Albari\u00f1o, C.G., Vargas, J., Comer, J.A., Rollin, P.E., and Ksiazek, T.G. (2008). Chapare virus, a newly discovered arenavirus isolated from a fatal hemorrhagic fever case in Bolivia. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000047"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1590\/0037-8682-0330-2016","article-title":"Keeping track of hidden dangers\u2014The short history of the Sabia virus","volume":"50","author":"Ellwanger","year":"2017","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Escalera-Antezana, J.P., Rodriguez-Villena, O.J., Arancibia-Alba, A.W., Alvarado-Arnez, L.E., Bonilla-Aldana, D.K., and Rodr\u00edguez-Morales, A.J. (2020). Clinical features of fatal cases of Chapare virus hemorrhagic fever originating from rural La Paz, Bolivia, 2019: A cluster analysis. Travel Med. Infect. Dis., 101589.","DOI":"10.1016\/j.tmaid.2020.101589"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.3201\/eid2606.200099","article-title":"Sabi\u00e1 virus-like mammarenavirus in patient with fatal hemorrhagic fever, Brazil, 2020","volume":"26","author":"Amgarten","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1097\/00006454-199906000-00013","article-title":"Lymphocytic choriomeningitis virus: Pediatric pathogen and fetal teratogen","volume":"18","author":"Barton","year":"1999","journal-title":"Pediatric Infect. Dis. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1086\/321897","article-title":"Congenital lymphocytic choriomeningitis virus infection: Decade of rediscovery","volume":"33","author":"Barton","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1067\/mob.2002.126297","article-title":"Lymphocytic choriomeningitis virus: Emerging fetal teratogen","volume":"187","author":"Barton","year":"2002","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_15","first-page":"486","article-title":"Lymphocytic choriomeningitis virus. A neglected pathogen of man","volume":"116","author":"Jahrling","year":"1992","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1056\/NEJMp068021","article-title":"Lymphocytic choriomeningitis virus\u2014An old enemy up to new tricks","volume":"354","author":"Peters","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1086\/514211","article-title":"AHF Study Group, Protective efficacy of a live attenuated vaccine against Argentine hemorrhagic fever","volume":"177","author":"Maiztegui","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0065-3527(02)58004-0","article-title":"Treatment of arenavirus infections: From basic studies to the challenge of antiviral therapy","volume":"58","author":"Damonte","year":"2002","journal-title":"Adv. Virus Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7246","DOI":"10.1128\/JVI.00614-11","article-title":"Ribavirin can be mutagenic for arenaviruses","volume":"85","author":"Moreno","year":"2011","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.virusres.2004.11.006","article-title":"Metabolism and antiviral activity of ribavirin","volume":"107","author":"Parker","year":"2005","journal-title":"Virus Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Gowen, B.B., Juelich, T.L., Sefing, E.J., Brasel, T., Smith, J.K., Zhang, L., Tigabu, B., Hill, T.E., Yun, T., and Pietzsch, C. (2013). Favipiravir (T-705) inhibits Jun\u00edn virus infection and reduces mortality in a guinea pig model of Argentine hemorrhagic fever. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002614"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1128\/AAC.01219-10","article-title":"T-705 (favipiravir) inhibition of arenavirus replication in cell culture","volume":"55","author":"Mendenhall","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mendenhall, M., Russell, A., Smee, D.F., Hall, J.O., Skirpstunas, R., Furuta, Y., and Gowen, B.B. (2011). Effective oral favipiravir (T-705) therapy initiated after the onset of clinical disease in a model of arenavirus hemorrhagic Fever. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001342"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14775","DOI":"10.1038\/srep14775","article-title":"The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset","volume":"5","author":"Safronetz","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104558","DOI":"10.1016\/j.antiviral.2019.104558","article-title":"The ReFRAME library as a comprehensive drug repurposing library to identify mammarenavirus inhibitors","volume":"169","author":"Kim","year":"2019","journal-title":"Antiviral Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41426-018-0191-1","article-title":"Novel AR-12 derivatives, P12-23 and P12-34, inhibit flavivirus replication by blocking host de novo pyrimidine biosynthesis","volume":"7","author":"Yang","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1083\/jcb.201107058","article-title":"Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export","volume":"196","author":"Zhang","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_28","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":"Antiviral Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5777","DOI":"10.1073\/pnas.1101143108","article-title":"Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis","volume":"108","author":"Hoffmann","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"111681","DOI":"10.1016\/j.ejmech.2019.111681","article-title":"Dihydroorotate dehydrogenase inhibitors in anti-infective drug research","volume":"183","author":"Boschi","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s40268-019-00286-z","article-title":"The selective oral immunomodulator vidofludimus in patients with active rheumatoid arthritis: Safety results from the COMPONENT study","volume":"19","author":"Muehler","year":"2019","journal-title":"Drugs R D"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e00383-17","DOI":"10.1128\/AAC.00383-17","article-title":"Original chemical series of pyrimidine biosynthesis inhibitors that boost the antiviral interferon response","volume":"61","author":"Dauzonne","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1128\/JVI.02102-10","article-title":"Rescue from cloned cDNAs and In Vivo characterization of recombinant pathogenic Romero and live-attenuated Candid #1 strains of Junin virus, the causative agent of Argentine hemorrhagic fever disease","volume":"85","author":"Emonet","year":"2011","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Iwasaki, M., Minder, P., Ca\u00ec, Y., Kuhn, J.H., Yates, J.R., Torbett, B.E., and de la Torre, J.C. (2018). Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na+\/K+ transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006892"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ca\u00ec, Y., Iwasaki, M., Beitzel, B.F., Y\u00fa, S., Postnikova, E.N., Cubitt, B., DeWald, L.E., Radoshitzky, S.R., Bollinger, L., and Jahrling, P.B. (2018). Recombinant Lassa virus expressing green fluorescent protein as a tool for high-throughput drug screens and neutralizing antibody assays. Viruses, 10.","DOI":"10.3390\/v10110655"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1021\/jm0506975","article-title":"Dual binding mode of a novel series of DHODH inhibitors","volume":"49","author":"Baumgartner","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4854","DOI":"10.1016\/j.bmcl.2005.07.053","article-title":"SAR, species specificity, and cellular activity of cyclopentene dicarboxylic acid amides as DHODH inhibitors","volume":"15","author":"Leban","year":"2005","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_38","first-page":"6","article-title":"Quantifizierung des Lympho-Choriomeningitis-Virus mit einer immunologischen Fokustechnik in 24- oder 96-Loch-Platten","volume":"10","author":"Battegay","year":"1993","journal-title":"ALTEX"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1128\/JVI.77.2.1184-1194.2003","article-title":"Characterization of the genomic promoter of the prototypic arenavirus lymphocytic choriomeningitis virus","volume":"77","author":"Perez","year":"2003","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.virol.2008.09.008","article-title":"A cell-based luciferase assay amenable to high-throughput screening of inhibitors of arenavirus budding","volume":"382","author":"Capul","year":"2008","journal-title":"Virology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/2049-632X.12171","article-title":"The NIAID Integrated Research Facility at Frederick, Maryland: A unique international resource to facilitate medical countermeasure development for BSL-4 pathogens","volume":"71","author":"Jahrling","year":"2014","journal-title":"Pathog. Dis."},{"key":"ref_42","first-page":"e52317","article-title":"Safety precautions and operating procedures in an (A)BSL-4 laboratory: 1. biosafety level 4 suit laboratory suite entry and exit procedures","volume":"116","author":"Janosko","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_43","first-page":"e53600","article-title":"Safety precautions and operating procedures in an (A)BSL-4 laboratory: 2. general practices","volume":"116","author":"Mazur","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_44","first-page":"5014","article-title":"Mechanism of action of the novel anticancer agent 6-fluoro-2-(2\u2032-fluoro-1,1\u2032-biphenyl-4-yl)-3-methyl-4-quinolinecarbo xylic acid sodium salt (NSC 368390): Inhibition of De Novo pyrimidine nucleotide biosynthesis","volume":"46","author":"Chen","year":"1986","journal-title":"Cancer Res."},{"key":"ref_45","first-page":"4644","article-title":"In Vivo inhibition of the pyrimidine De Novo enzyme dihydroorotic acid dehydrogenase by brequinar sodium (DUP-785; NSC 368390) in mice and patients","volume":"50","author":"Peters","year":"1990","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1080\/15257770.2018.1508692","article-title":"Re-evaluation of brequinar sodium, a dihydroorotate dehydrogenase inhibitor","volume":"37","author":"Peters","year":"2018","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10924","DOI":"10.1128\/JVI.01587-15","article-title":"Identification and mechanism of action of a novel small-molecule inhibitor of arenavirus multiplication","volume":"89","author":"Ngo","year":"2015","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Lucas-Hourani, M., Dauzonne, D., Jorda, P., Cousin, G., Lupan, A., Helynck, O., Caignard, G., Janvier, G., Andr\u00e9-Leroux, G., and Khiar, S. (2013). Inhibition of pyrimidine biosynthesis pathway suppresses viral growth through innate immunity. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003678"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4552","DOI":"10.1128\/AAC.00282-16","article-title":"Discovery of a broad-spectrum antiviral compound that inhibits pyrimidine biosynthesis and establishes a type 1 interferon-independent antiviral state","volume":"60","author":"Chung","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1073\/pnas.1019304108","article-title":"Point mutation in the glycoprotein of lymphocytic choriomeningitis virus is necessary for receptor binding, dendritic cell infection, and long-term persistence","volume":"108","author":"Sullivan","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7728","DOI":"10.1128\/JVI.00187-12","article-title":"Arenavirus nucleoprotein targets interferon regulatory factor-activating kinase IKK\u03b5","volume":"86","author":"Pythoud","year":"2012","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1099\/jgv.0.000758","article-title":"Broad-spectrum inhibition of common respiratory RNA viruses by a pyrimidine synthesis inhibitor with involvement of the host antiviral response","volume":"98","author":"Cheung","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1165\/rcmb.2007-0142OC","article-title":"Post-infection A77-1726 blocks pathophysiologic sequelae of respiratory syncytial virus infection","volume":"37","author":"Davis","year":"2007","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nchembio.2050","article-title":"Parallel shRNA and CRISPR-Cas9 screens enable antiviral drug target identification","volume":"12","author":"Deans","year":"2016","journal-title":"Nat. Chem. Biol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/8\/821\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:52:30Z","timestamp":1760176350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/8\/821"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,29]]},"references-count":54,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["v12080821"],"URL":"https:\/\/doi.org\/10.3390\/v12080821","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,29]]}}}