{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T17:02:06Z","timestamp":1789405326940,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T00:00:00Z","timestamp":1666396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["1R21-AI-146503-01A1"],"award-info":[{"award-number":["1R21-AI-146503-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["465425\/2014-3"],"award-info":[{"award-number":["465425\/2014-3"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Science and Technology (INCT) in Dengue and host-microbial interactions","award":["1R21-AI-146503-01A1"],"award-info":[{"award-number":["1R21-AI-146503-01A1"]}]},{"name":"National Institute of Science and Technology (INCT) in Dengue and host-microbial interactions","award":["465425\/2014-3"],"award-info":[{"award-number":["465425\/2014-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Yellow fever virus (YFV) is a potentially lethal, zoonotic, blood-borne flavivirus transmitted to humans and non-human primates by mosquitoes. Owing to multiple deadly epidemics, the WHO classifies YFV as a \u201chigh impact, high threat disease\u201d with resurgent epidemic potential. At present, there are no approved antiviral therapies to combat YFV infection. Herein we report on 2\u2032-halogen-modified nucleoside analogs as potential anti-YFV agents. Of 11 compounds evaluated, three showed great promise with low toxicity, high intracellular metabolism into the active nucleoside triphosphate form, and sub-micromolar anti-YFV activity. Notably, we investigated a 2\u2032-fluoro,2\u2032-bromouridine phosphate prodrug (C9), a known anti-HCV agent with good stability in human blood and favorable metabolism. Predictive modeling revealed that C9 could readily bind the active site of the YFV RdRp, conferring its anti-YFV activity. C9 displayed potent anti-YFV activity in primary human macrophages, 3D hepatocyte spheroids, and in mice. In an A129 murine model, shortly after infection, C9 significantly reduced YFV replication and protected against YFV-induced liver inflammation and pathology with no adverse effects. Collectively, this work identifies a potent new anti-YFV agent with strong therapeutic promise.<\/jats:p>","DOI":"10.3390\/microorganisms10112098","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T06:37:45Z","timestamp":1666593465000},"page":"2098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Discovery of a 2\u2032-Fluoro,2\u2032-Bromouridine Phosphoramidate Prodrug Exhibiting Anti-Yellow Fever Virus Activity in Culture and in Mice"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0056-176X","authenticated-orcid":false,"given":"Julia C.","family":"LeCher","sequence":"first","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keivan","family":"Zandi","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian Vasconcelos","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Morphology, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Amblard","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Tao","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1601-256X","authenticated-orcid":false,"given":"Dharmeshkumar","family":"Patel","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujin","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8392-1467","authenticated-orcid":false,"given":"Felipe Rocha","family":"da Silva Santos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus Rodrigues","family":"Goncalves","sequence":"additional","affiliation":[{"name":"Department of Morphology, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso Martins","family":"Queroz-Junior","sequence":"additional","affiliation":[{"name":"Department of Morphology, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Martins","family":"Marim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1857-8818","authenticated-orcid":false,"given":"Katie","family":"Musall","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu Ling","family":"Goh","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"McBrayer","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Downs-Bowen","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramyani","family":"De","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niloufar","family":"Azadi","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Kohler","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6944-3008","authenticated-orcid":false,"given":"Mauro Martins","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Department of Morphology, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond F.","family":"Schinazi","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,22]]},"reference":[{"key":"ref_1","unstructured":"Pan American Health Organization (2021, November 10). Yellow Fever. Available online: https:\/\/www.paho.org\/en\/topics\/yellow-fever."},{"key":"ref_2","unstructured":"Center for Disease Control and Prevention (2021, November 10). Yellow Fever, Available online: https:\/\/www.cdc.gov\/yellowfever\/index.html."},{"key":"ref_3","unstructured":"World Health Organization (2021, November 10). World Health Organization Initiative: Eliminate Yellow Fever (EYE) Epidemics 2017\u20132026. Available online: https:\/\/www.who.int\/initiatives\/eye-strategy."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Servadio, J.L., Munoz-Zanzi, C., and Convertino, M. (2021). Estimating case fatality risk of severe yellow fever cases: Systematic literature review and meta-analysis. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06535-4"},{"key":"ref_5","unstructured":"Knipe, D.M.a.H., and Peter, M. (2007). Flaviviruses. Fields Virology, Lippincott Williams & Williams. [5th ed.]."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.antiviral.2018.04.004","article-title":"The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold","volume":"154","author":"Yates","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.antiviral.2018.11.016","article-title":"The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: Complex modifications to the nucleoside scaffold","volume":"162","author":"Yates","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1177\/095632020601700203","article-title":"Inhibition of hepatitis C replicon RNA synthesis by beta-D-2\u2032-deoxy-2\u2032-fluoro-2\u2032-C-methylcytidine: A specific inhibitor of hepatitis C virus replication","volume":"17","author":"Stuyver","year":"2006","journal-title":"Antivir. Chem. Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.aohep.2019.09.001","article-title":"Sofosbuvir inhibits yellow fever virus in vitro and in patients with acute liver failure","volume":"18","author":"Mendes","year":"2019","journal-title":"Ann. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"de Freitas, C.S., Higa, L.M., Sacramento, C.Q., Ferreira, A.C., Reis, P.A., Delvecchio, R., Monteiro, F.L., Barbosa-Lima, G., James Westgarth, H., and Vieira, Y.R. (2019). Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007072"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e00889-19","DOI":"10.1128\/AAC.00889-19","article-title":"Nucleoside analogs with antiviral activity against yellow fever virus","volume":"63","author":"Zandi","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5424","DOI":"10.1021\/acs.jmedchem.7b00067","article-title":"2\u2032-chloro,2\u2032-fluoro ribonucleotide prodrugs with potent pan-genotypic activity against hepatitis C virus replication in culture","volume":"60","author":"Zhou","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1021\/acs.jmedchem.8b01300","article-title":"Discovery of a series of 2\u2032-alpha-fluoro,2\u2032-beta-bromo-ribonucleosides and their phosphoramidate prodrugs as potent pan-genotypic inhibitors of hepatitis C virus","volume":"62","author":"Mengshetti","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.1016\/j.bmcl.2017.05.075","article-title":"Discovery of beta-D-2\u2032-deoxy-2\u2032-dichlorouridine nucleotide prodrugs as potent inhibitors of hepatitis C virus replication","volume":"27","author":"Pinho","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.nbd.2016.02.007","article-title":"The Janus kinase inhibitor ruxolitinib reduces HIV replication in human macrophages and ameliorates HIV encephalitis in a murine model","volume":"92","author":"Haile","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/imm.13125","article-title":"Monocyte isolation techniques significantly impact the phenotype of both isolated monocytes and derived macrophages in vitro","volume":"159","author":"Nielsen","year":"2020","journal-title":"Immunology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e01652-20","DOI":"10.1128\/AAC.01652-20","article-title":"Repurposing nucleoside analogs for human coronaviruses","volume":"65","author":"Zandi","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cong, Y., McArthur, M.A., Cohen, M., Jahrling, P.B., Janosko, K.B., Josleyn, N., Kang, K., Zhang, T., and Holbrook, M.R. (2016). Characterization of yellow fever virus infection of human and non-human primate antigen presenting cells and their interaction with CD4+ T cells. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004709"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.bmc.2019.01.005","article-title":"Synthesis and anti-HCV activity of beta-D-2\u2032-deoxy-2\u2032-alpha-chloro-2\u2032-beta-fluoro and beta-D-2\u2032-deoxy-2\u2032-alpha-bromo-2\u2032-beta-fluoro nucleosides and their phosphoramidate prodrugs","volume":"27","author":"Ovadia","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5296","DOI":"10.1016\/j.bmcl.2017.10.024","article-title":"Synthesis and anti-HCV activity of a series of beta-D-2\u2032-deoxy-2\u2032-dibromo nucleosides and their corresponding phosphoramidate prodrugs","volume":"27","author":"Chen","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3727\/095535491820873191","article-title":"Use of an aqueous soluble tetrazolium\/formazan assay for cell growth assays in culture","volume":"3","author":"Cory","year":"1991","journal-title":"Cancer Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv. Enzym. Regul."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100045","DOI":"10.1016\/j.crphar.2021.100045","article-title":"Comparison of anti-SARS-CoV-2 activity and intracellular metabolism of remdesivir and its parent nucleoside","volume":"2","author":"Tao","year":"2021","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1080\/15257770.2019.1671594","article-title":"Intracellular metabolism and potential cardiotoxicity of a beta-D-2\u2032-C-methyl-2,6-diaminopurine ribonucleoside phosphoramidate that inhibits hepatitis C virus replication","volume":"39","author":"Tao","year":"2020","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5284","DOI":"10.1021\/jm040068f","article-title":"Structure-activity relationship of heterobase-modified 2\u2032-C-methyl ribonucleosides as inhibitors of hepatitis C virus RNA replication","volume":"47","author":"Eldrup","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3944","DOI":"10.1128\/AAC.48.10.3944-3953.2004","article-title":"A 7-deaza-adenosine analog is a potent and selective inhibitor of hepatitis C virus replication with excellent pharmacokinetic properties","volume":"48","author":"Olsen","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5504","DOI":"10.1021\/jm0502788","article-title":"Design, synthesis, and antiviral activity of 2\u2032-deoxy-2\u2032-fluoro-2\u2032-C-methylcytidine, a potent inhibitor of hepatitis C virus replication","volume":"48","author":"Clark","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11979","DOI":"10.1074\/jbc.M210914200","article-title":"Inhibition of hepatitis C virus RNA replication by 2\u2032-modified nucleoside analogs","volume":"278","author":"Carroll","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1081\/NCN-200060112","article-title":"NM-283, an efficient prodrug of the potent anti-HCV agent 2\u2032-C-methylcytidine","volume":"24","author":"Pierra","year":"2005","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1128\/AAC.00400-06","article-title":"Mechanism of activation of beta-D-2\u2032-deoxy-2\u2032-fluoro-2\u2032-C-methylcytidine and inhibition of hepatitis C virus NS5B RNA polymerase","volume":"51","author":"Murakami","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7202","DOI":"10.1021\/jm100863x","article-title":"Discovery of a beta-D-2\u2032-deoxy-2\u2032-alpha-fluoro-2\u2032-beta-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus","volume":"53","author":"Sofia","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"104536","DOI":"10.1016\/j.antiviral.2019.104536","article-title":"Structure of the yellow fever NS5 protein reveals conserved drug targets shared among flaviviruses","volume":"169","author":"Dubankova","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1089\/adt.2014.573","article-title":"Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors","volume":"12","author":"Edmondson","year":"2014","journal-title":"Assay Drug Dev. Technol."},{"key":"ref_34","first-page":"1","article-title":"Two-dimensional (2D) and three-dimensional (3D) cell culturing in drug discovery","volume":"Volume 2","author":"Mehanna","year":"2018","journal-title":"Cell Culture"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Meier, K.C., Gardner, C.L., Khoretonenko, M.V., Klimstra, W.B., and Ryman, K.D. (2009). A mouse model for studying viscerotropic disease caused by yellow fever virus infection. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000614"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/hep4.1504","article-title":"Molecular mechanism for protection against liver failure in human yellow fever infection","volume":"4","author":"Lemos","year":"2020","journal-title":"Hepatol. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.antiviral.2013.11.008","article-title":"Chutes and ladders in hepatitis C nucleoside drug development","volume":"102","author":"Coats","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1021\/acsomega.1c06174","article-title":"Diastereoselective synthesis of 2\u2032-dihalopyrimidine ribonucleoside inhibitors of hepatitis C virus replication","volume":"7","author":"Zhou","year":"2022","journal-title":"ACS Omega"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"104855","DOI":"10.1016\/j.antiviral.2020.104855","article-title":"7-Deaza-7-fluoro-2\u2032-C-methyladenosine inhibits Zika virus infection and viral-induced neuroinflammation","volume":"180","author":"Rocha","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e00397-19","DOI":"10.1128\/AAC.00397-19","article-title":"Nucleoside analogs with selective antiviral activity against dengue fever and Japanese encephalitis viruses","volume":"63","author":"Zandi","year":"2019","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/11\/2098\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:00:52Z","timestamp":1760144452000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/11\/2098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,22]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["microorganisms10112098"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms10112098","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,22]]}}}