{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T19:20:29Z","timestamp":1772220029445,"version":"3.50.1"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R56AI156137-01"],"award-info":[{"award-number":["1R56AI156137-01"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR073964"],"award-info":[{"award-number":["R01AR073964"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR081489"],"award-info":[{"award-number":["R01AR081489"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000147","name":"Division of Civil, Mechanical and Manufacturing Innovation","doi-asserted-by":"publisher","award":["1554708"],"award-info":[{"award-number":["1554708"]}],"id":[{"id":"10.13039\/100000147","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Viral infections induce major shifts in cellular metabolism elicited by active viral replication and antiviral responses. For the virus, harnessing cellular metabolism and evading changes that limit replication are essential for productive viral replication. In contrast, the cellular response to infection disrupts metabolic pathways to prevent viral replication and promote an antiviral state in the host cell and neighboring bystander cells. This competition between the virus and cell results in measurable shifts in cellular metabolism that differ depending on the virus, cell type, and extracellular environment. The resulting metabolic shifts can be observed and analyzed using global metabolic profiling techniques to identify pathways that are critical for either viral replication or cellular defense. SARS-CoV-2 is a respiratory virus that can exhibit broad tissue tropism and diverse, yet inconsistent, symptomatology. While the factors that determine the presentation and severity of SARS-CoV-2 infection remain unclear, metabolic syndromes are associated with more severe manifestations of SARS-CoV-2 disease. Despite these observations a critical knowledge gap remains between cellular metabolic responses and SARS-CoV-2 infection. Using a well-established untargeted metabolomics analysis workflow, we compared SARS-CoV-2 infection of human lung carcinoma cells. We identified significant changes in metabolic pathways that correlate with either productive or non-productive viral infection. This information is critical for characterizing the factors that contribute to SARS-CoV-2 replication that could be targeted for therapeutic interventions to limit viral disease.<\/jats:p>","DOI":"10.1371\/journal.pone.0305065","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T13:43:11Z","timestamp":1739367791000},"page":"e0305065","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Starve a cold or feed a fever? Identifying cellular metabolic changes following infection and exposure to SARS-CoV-2"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1154-7728","authenticated-orcid":true,"given":"Emma K.","family":"Loveday","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hope","family":"Welhaven","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8853-1345","authenticated-orcid":true,"given":"Ayten Ebru","family":"Erdogan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle S.","family":"Hain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke F.","family":"Domanico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9555-8223","authenticated-orcid":true,"given":"Connie B.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0752-4109","authenticated-orcid":true,"given":"Ronald K.","family":"June","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0199-7175","authenticated-orcid":true,"given":"Matthew P.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"issue":"1","key":"pone.0305065.ref001","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12915-019-0678-9","article-title":"Viral hijacking of cellular metabolism","volume":"17","author":"SK Thaker","year":"2019","journal-title":"BMC Biol"},{"key":"pone.0305065.ref002","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.virol.2015.02.038","article-title":"Viral activation of cellular metabolism","author":"EL Sanchez","year":"2015","journal-title":"Virology"},{"issue":"10","key":"pone.0305065.ref003","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/s42255-022-00652-3","article-title":"Innate metabolic responses against viral infections","volume":"4","author":"CS Palmer","year":"2022","journal-title":"Nat Metab"},{"key":"pone.0305065.ref004","doi-asserted-by":"crossref","first-page":"725043","DOI":"10.3389\/fcimb.2021.725043","article-title":"The role of tricarboxylic acid cycle metabolites in viral infections","volume":"11","author":"FJ S\u00e1nchez-Garc\u00eda","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0305065.ref005","doi-asserted-by":"crossref","first-page":"8873","DOI":"10.1038\/ncomms9873","article-title":"MYC-induced reprogramming of glutamine catabolism supports optimal virus replication","volume":"6","author":"M Thai","year":"2015","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0305065.ref006","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s42255-021-00507-3","article-title":"Viral infection as an NAD+ battlefield","volume":"4","author":"C Brenner","year":"2022","journal-title":"Nat Metab"},{"key":"pone.0305065.ref007","doi-asserted-by":"crossref","first-page":"e210003","DOI":"10.20900\/immunometab20210003","article-title":"Pathogens hijack host cell metabolism: intracellular infection as a driver of the Warburg effect in cancer and other chronic inflammatory conditions","volume":"3","author":"AD Proal","year":"2021","journal-title":"Immunometabolism"},{"issue":"1","key":"pone.0305065.ref008","doi-asserted-by":"crossref","first-page":"9110","DOI":"10.1038\/s41598-017-09536-z","article-title":"Altered lipid metabolism in recovered SARS patients twelve years after infection","volume":"7","author":"Q Wu","year":"2017","journal-title":"Sci Rep"},{"issue":"2","key":"pone.0305065.ref009","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1021\/acs.jproteome.0c00876","article-title":"NMR spectroscopic windows on the systemic effects of SARS-CoV-2 infection on plasma lipoproteins and metabolites in relation to circulating cytokines","volume":"20","author":"S Lodge","year":"2021","journal-title":"J Proteome Res"},{"key":"pone.0305065.ref010","doi-asserted-by":"crossref","first-page":"e0033821","DOI":"10.1128\/spectrum.00338-21","article-title":"Amino acid metabolism is significantly altered at the time of admission in hospital for severe COVID-19 patients: findings from longitudinal targeted metabolomics analysis","volume":"9","author":"L Ansone","year":"2021","journal-title":"Microbiol Spectr"},{"issue":"25","key":"pone.0305065.ref011","doi-asserted-by":"crossref","first-page":"e2101708118","DOI":"10.1073\/pnas.2101708118","article-title":"Altered amino acid profile in patients with SARS-CoV-2 infection","volume":"118","author":"CA Rees","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"pone.0305065.ref012","doi-asserted-by":"crossref","first-page":"4428","DOI":"10.1021\/acs.jproteome.0c00537","article-title":"Quantitative In-Vitro diagnostic NMR spectroscopy for lipoprotein and metabolite measurements in plasma and serum: recommendations for analytical artifact minimization with special reference to COVID-19\/SARS-CoV-2 samples","volume":"19","author":"RL Loo","year":"2020","journal-title":"J Proteome Res"},{"key":"pone.0305065.ref013","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.bbrc.2018.03.117","article-title":"Application of global metabolomic profiling of synovial fluid for osteoarthritis biomarkers","volume":"499","author":"A Carlson","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"issue":"8","key":"pone.0305065.ref014","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.joca.2019.04.007","article-title":"Characterization of synovial fluid metabolomic phenotypes of cartilage morphological changes associated with osteoarthritis","volume":"27","author":"AK Carlson","year":"2019","journal-title":"Osteoarthritis Cartilage"},{"issue":"1","key":"pone.0305065.ref015","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cmet.2021.11.005","article-title":"Metabolite discovery: Biochemistry\u2019s scientific driver","volume":"34","author":"M Giera","year":"2022","journal-title":"Cell Metab"},{"key":"pone.0305065.ref016","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1038\/s41467-021-21903-z","article-title":"SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication","volume":"12","author":"Y Zhang","year":"2021","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0305065.ref017","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1038\/s41467-021-22166-4","article-title":"SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition","volume":"12","author":"PJ Mullen","year":"2021","journal-title":"Nat Commun"},{"issue":"11","key":"pone.0305065.ref018","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.3390\/v11111007","article-title":"Metabolomic analysis of influenza a virus A\/WSN\/1933 (H1N1) infected A549 cells during first cycle of viral replication","volume":"11","author":"X Tian","year":"2019","journal-title":"Viruses"},{"issue":"5","key":"pone.0305065.ref019","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.cell.2020.04.026","article-title":"Imbalanced host response to SARS-CoV-2 drives development of COVID-19","volume":"181","author":"D Blanco-Melo","year":"2020","journal-title":"Cell"},{"issue":"2","key":"pone.0305065.ref020","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","volume":"181","author":"M Hoffmann","year":"2020","journal-title":"Cell"},{"key":"pone.0305065.ref021","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.1128\/JVI.79.6.3846-3850.2005","article-title":"Exogenous ACE2 expression allows refractory cell lines to support severe acute respiratory syndrome coronavirus replication","volume":"79","author":"EC Mossel","year":"2005","journal-title":"J Virol"},{"issue":"3","key":"pone.0305065.ref022","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.tem.2021.01.001","article-title":"Altered cholesterol and lipid synthesis mediates Hyperinflammation in COVID-19","volume":"32","author":"Y Sohrabi","year":"2021","journal-title":"Trends Endocrinol Metab"},{"issue":"1","key":"pone.0305065.ref023","doi-asserted-by":"crossref","first-page":"6350","DOI":"10.1038\/s41598-021-85788-0","article-title":"Metabolomics analysis reveals a modified amino acid metabolism that correlates with altered oxygen homeostasis in COVID-19 patients","volume":"11","author":"JC P\u00e1ez-Franco","year":"2021","journal-title":"Sci Rep"},{"issue":"12","key":"pone.0305065.ref024","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1038\/s41418-021-00892-y","article-title":"Comorbidity-associated glutamine deficiency is a predisposition to severe COVID-19","volume":"28","author":"T Matsuyama","year":"2021","journal-title":"Cell Death Differ"},{"key":"pone.0305065.ref025","article-title":"COVID-19 infection results in alterations of the kynurenine pathway and fatty acid metabolism that correlate with IL-6 levels and renal status","author":"T Thomas","year":"2020","journal-title":"medRxiv"},{"issue":"2","key":"pone.0305065.ref026","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3390\/metabo13020263","article-title":"Salivary metabolomic analysis reveals amino acid metabolism shift in SARS-CoV-2 virus activity and post-infection condition","volume":"13","author":"TK da Silva Fidalgo","year":"2023","journal-title":"Metabolites"},{"issue":"1","key":"pone.0305065.ref027","doi-asserted-by":"crossref","first-page":"16824","DOI":"10.1038\/s41598-020-73966-5","article-title":"The specific metabolome profiling of patients infected by SARS-COV-2 supports the key role of tryptophan-nicotinamide pathway and cytosine metabolism","volume":"10","author":"H Blasco","year":"2020","journal-title":"Sci Rep"},{"issue":"6","key":"pone.0305065.ref028","doi-asserted-by":"crossref","first-page":"622","DOI":"10.3390\/v12060622","article-title":"Propagation, inactivation, and safety testing of SARS-CoV-2","volume":"12","author":"AS Jureka","year":"2020","journal-title":"Viruses"},{"key":"pone.0305065.ref029","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/175352a0","article-title":"Use of methyl cellulose gel as a substitute for agar in tissue-culture overlays","volume":"175","author":"JE Hotchin","year":"1955","journal-title":"Nature"},{"issue":"5","key":"pone.0305065.ref030","doi-asserted-by":"crossref","first-page":"e156","DOI":"10.1371\/journal.pbio.0030156","article-title":"Subversion of cellular autophagosomal machinery by RNA viruses","volume":"3","author":"WT Jackson","year":"2005","journal-title":"PLoS Biol"},{"key":"pone.0305065.ref031","first-page":"14.10.1-14.10.91","article-title":"Using MetaboAnalyst 3.0 for comprehensive metabolomics data analysis","volume":"55","author":"J Xia","year":"2016","journal-title":"Curr Protoc Bioinformatics"},{"key":"pone.0305065.ref032","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1038\/s41596-022-00710-w","article-title":"Using MetaboAnalyst 5.0 for LC\u2013HRMS spectra processing, multi-omics integration and covariate adjustment of global metabolomics data","volume":"17","author":"Z Pang","year":"2022","journal-title":"Nature Protocols"},{"issue":"W1","key":"pone.0305065.ref033","doi-asserted-by":"crossref","first-page":"W486","DOI":"10.1093\/nar\/gky310","article-title":"MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis","volume":"46","author":"J Chong","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"pone.0305065.ref034","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1099\/jgv.0.001453","article-title":"SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology","volume":"101","author":"NS Ogando","year":"2020","journal-title":"J Gen Virol"},{"issue":"5","key":"pone.0305065.ref035","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.1021\/acs.analchem.7b04424","article-title":"METLIN: a technology platform for identifying knowns and unknowns","volume":"90","author":"C Guijas","year":"2018","journal-title":"Anal Chem"},{"issue":"3","key":"pone.0305065.ref036","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.cell.2015.07.016","article-title":"An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis","volume":"162","author":"K Birsoy","year":"2015","journal-title":"Cell"},{"issue":"3","key":"pone.0305065.ref037","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.cell.2015.07.017","article-title":"Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells","volume":"162","author":"LB Sullivan","year":"2015","journal-title":"Cell"},{"issue":"5","key":"pone.0305065.ref038","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1021\/acs.jproteome.1c00052","article-title":"Systemic perturbations in amine and kynurenine metabolism associated with acute SARS-CoV-2 infection and inflammatory cytokine responses","volume":"20","author":"NG Lawler","year":"2021","journal-title":"J Proteome Res"},{"issue":"17","key":"pone.0305065.ref039","doi-asserted-by":"crossref","first-page":"9548","DOI":"10.3390\/ijms22179548","article-title":"The serum metabolome of moderate and severe COVID-19 patients reflects possible liver alterations involving carbon and nitrogen metabolism","volume":"22","author":"M Caterino","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"7","key":"pone.0305065.ref040","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/s42255-020-0237-2","article-title":"A metabolic handbook for the COVID-19 pandemic","volume":"2","author":"JS Ayres","year":"2020","journal-title":"Nat Metab"},{"issue":"7","key":"pone.0305065.ref041","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1093\/nsr\/nwaa086","article-title":"Plasma metabolomic and lipidomic alterations associated with COVID-19","volume":"7","author":"D Wu","year":"2020","journal-title":"Natl Sci Rev"},{"key":"pone.0305065.ref042","doi-asserted-by":"crossref","first-page":"154739","DOI":"10.1016\/j.metabol.2021.154739","article-title":"The serum metabolome of COVID-19 patients is distinctive and predictive","volume":"118","author":"D Shi","year":"2021","journal-title":"Metabolism"},{"issue":"4","key":"pone.0305065.ref043","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41419-023-05791-3","article-title":"Plasma metabolomic characterization of SARS-CoV-2 Omicron infection","volume":"14","author":"X Li","year":"2023","journal-title":"Cell Death Dis"},{"issue":"10","key":"pone.0305065.ref044","doi-asserted-by":"crossref","first-page":"101645","DOI":"10.1016\/j.isci.2020.101645","article-title":"SARS-CoV-2 infection dysregulates the metabolomic and lipidomic profiles of serum","volume":"23","author":"C Bruzzone","year":"2020","journal-title":"iScience"},{"issue":"2","key":"pone.0305065.ref045","doi-asserted-by":"crossref","first-page":"e0219422","DOI":"10.1128\/spectrum.02194-22","article-title":"Integrated metabolic and inflammatory signatures associated with severity of, fatality of, and recovery from COVID-19","volume":"11","author":"LG Gardinassi","year":"2023","journal-title":"Microbiol Spectr"},{"key":"pone.0305065.ref046","doi-asserted-by":"crossref","first-page":"106966","DOI":"10.1016\/j.ymgme.2022.106966","article-title":"The multiple facets of acetyl-CoA metabolism: energetics, biosynthesis, regulation, acylation and inborn errors","volume":"138","author":"Y Wang","year":"2023","journal-title":"Mol Genet Metab"},{"issue":"39","key":"pone.0305065.ref047","doi-asserted-by":"crossref","first-page":"5483","DOI":"10.1021\/acs.biochem.6b00342","article-title":"Cholesterol biosynthesis: a mechanistic overview","volume":"55","author":"NMFSA Cerqueira","year":"2016","journal-title":"Biochemistry"},{"key":"pone.0305065.ref048","doi-asserted-by":"crossref","first-page":"102174","DOI":"10.1016\/j.plefa.2020.102174","article-title":"Leukotrienes, a potential target for Covid-19","volume":"161","author":"F Citron","year":"2020","journal-title":"Prostaglandins Leukot Essent Fatty Acids"},{"issue":"6","key":"pone.0305065.ref049","first-page":"e21666","article-title":"High levels of eicosanoids and docosanoids in the lungs of intubated COVID-19 patients","volume":"35","author":"A-S Archambault","year":"2021","journal-title":"FASEB J"},{"key":"pone.0305065.ref050","doi-asserted-by":"crossref","first-page":"250","DOI":"10.4049\/jimmunol.2200079","article-title":"Acetylcholine, fatty acids, and lipid mediators are linked to COVID-19 severity","volume":"209","author":"MM P\u00e9rez","year":"2022","journal-title":"J Immunol"},{"issue":"3","key":"pone.0305065.ref051","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrm.2017.107","article-title":"Sphingolipids and their metabolism in physiology and disease","volume":"19","author":"YA Hannun","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"1","key":"pone.0305065.ref052","doi-asserted-by":"crossref","first-page":"e202101168","DOI":"10.26508\/lsa.202101168","article-title":"Elevation in sphingolipid upon SARS-CoV-2 infection: possible implications for COVID-19 pathology","volume":"5","author":"EB Vitner","year":"2021","journal-title":"Life Sci Alliance"},{"issue":"19","key":"pone.0305065.ref053","doi-asserted-by":"crossref","first-page":"10198","DOI":"10.3390\/ijms221910198","article-title":"Severity of COVID-19 patients predicted by serum sphingolipids signature","volume":"22","author":"E Torretta","year":"2021","journal-title":"Int J Mol Sci"},{"key":"pone.0305065.ref054","doi-asserted-by":"crossref","first-page":"630","DOI":"10.3389\/fimmu.2016.00630","article-title":"Effects of interferons and viruses on metabolism","volume":"7","author":"SD Fritsch","year":"2016","journal-title":"Front Immunol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0305065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T13:43:29Z","timestamp":1739367809000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0305065"}},"subtitle":[],"editor":[{"given":"Arunava","family":"Roy","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,2,12]]},"references-count":54,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0305065","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.05.22.595410","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,12]]}}}