{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T20:33:34Z","timestamp":1769632414407,"version":"3.49.0"},"reference-count":85,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2020\/03639-6"],"award-info":[{"award-number":["2020\/03639-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2020\/12875-5"],"award-info":[{"award-number":["2020\/12875-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2023\/09590-7"],"award-info":[{"award-number":["2023\/09590-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2017\/13341-1"],"award-info":[{"award-number":["2017\/13341-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2018\/15083-2"],"award-info":[{"award-number":["2018\/15083-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2013\/21719-3"],"award-info":[{"award-number":["2013\/21719-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2018\/24069-3"],"award-info":[{"award-number":["2018\/24069-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2018\/06510-4"],"award-info":[{"award-number":["2018\/06510-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2020\/08615-8"],"award-info":[{"award-number":["2020\/08615-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["309940\/2019-2"],"award-info":[{"award-number":["309940\/2019-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["U01AI151807"],"award-info":[{"award-number":["U01AI151807"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["405786\/2022-0"],"award-info":[{"award-number":["405786\/2022-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2020\/03639-6"],"award-info":[{"award-number":["2020\/03639-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2020\/12875-5"],"award-info":[{"award-number":["2020\/12875-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2023\/09590-7"],"award-info":[{"award-number":["2023\/09590-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2017\/13341-1"],"award-info":[{"award-number":["2017\/13341-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2018\/15083-2"],"award-info":[{"award-number":["2018\/15083-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2013\/21719-3"],"award-info":[{"award-number":["2013\/21719-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2018\/24069-3"],"award-info":[{"award-number":["2018\/24069-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2018\/06510-4"],"award-info":[{"award-number":["2018\/06510-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2020\/08615-8"],"award-info":[{"award-number":["2020\/08615-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["309940\/2019-2"],"award-info":[{"award-number":["309940\/2019-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["U01AI151807"],"award-info":[{"award-number":["U01AI151807"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["405786\/2022-0"],"award-info":[{"award-number":["405786\/2022-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health (NIH\/USA)","award":["2020\/03639-6"],"award-info":[{"award-number":["2020\/03639-6"]}]},{"name":"National Institutes of Health (NIH\/USA)","award":["2020\/12875-5"],"award-info":[{"award-number":["2020\/12875-5"]}]},{"name":"National Institutes of Health (NIH\/USA)","award":["2023\/09590-7"],"award-info":[{"award-number":["2023\/09590-7"]}]},{"name":"National Institutes of Health (NIH\/USA)","award":["2017\/13341-1"],"award-info":[{"award-number":["2017\/13341-1"]}]},{"name":"National Institutes of Health (NIH\/USA)","award":["2018\/15083-2"],"award-info":[{"award-number":["2018\/15083-2"]}]},{"name":"National Institutes of Health (NIH\/USA)","award":["2013\/21719-3"],"award-info":[{"award-number":["2013\/21719-3"]}]},{"name":"National Institutes of Health (NIH\/USA)","award":["2018\/24069-3"],"award-info":[{"award-number":["2018\/24069-3"]}]},{"name":"National Institutes of Health (NIH\/USA)","award":["2018\/06510-4"],"award-info":[{"award-number":["2018\/06510-4"]}]},{"name":"National Institutes of Health (NIH\/USA)","award":["2020\/08615-8"],"award-info":[{"award-number":["2020\/08615-8"]}]},{"name":"National Institutes of Health (NIH\/USA)","award":["309940\/2019-2"],"award-info":[{"award-number":["309940\/2019-2"]}]},{"name":"National Institutes of Health (NIH\/USA)","award":["U01AI151807"],"award-info":[{"award-number":["U01AI151807"]}]},{"name":"National Institutes of Health (NIH\/USA)","award":["405786\/2022-0"],"award-info":[{"award-number":["405786\/2022-0"]}]},{"name":"INCT Viral Genomic Surveillance and One Health","award":["2020\/03639-6"],"award-info":[{"award-number":["2020\/03639-6"]}]},{"name":"INCT Viral Genomic Surveillance and One Health","award":["2020\/12875-5"],"award-info":[{"award-number":["2020\/12875-5"]}]},{"name":"INCT Viral Genomic Surveillance and One Health","award":["2023\/09590-7"],"award-info":[{"award-number":["2023\/09590-7"]}]},{"name":"INCT Viral Genomic Surveillance and One Health","award":["2017\/13341-1"],"award-info":[{"award-number":["2017\/13341-1"]}]},{"name":"INCT Viral Genomic Surveillance and One Health","award":["2018\/15083-2"],"award-info":[{"award-number":["2018\/15083-2"]}]},{"name":"INCT Viral Genomic Surveillance and One Health","award":["2013\/21719-3"],"award-info":[{"award-number":["2013\/21719-3"]}]},{"name":"INCT Viral Genomic Surveillance and One Health","award":["2018\/24069-3"],"award-info":[{"award-number":["2018\/24069-3"]}]},{"name":"INCT Viral Genomic Surveillance and One Health","award":["2018\/06510-4"],"award-info":[{"award-number":["2018\/06510-4"]}]},{"name":"INCT Viral Genomic Surveillance and One Health","award":["2020\/08615-8"],"award-info":[{"award-number":["2020\/08615-8"]}]},{"name":"INCT Viral Genomic Surveillance and One Health","award":["309940\/2019-2"],"award-info":[{"award-number":["309940\/2019-2"]}]},{"name":"INCT Viral Genomic Surveillance and One Health","award":["U01AI151807"],"award-info":[{"award-number":["U01AI151807"]}]},{"name":"INCT Viral Genomic Surveillance and One Health","award":["405786\/2022-0"],"award-info":[{"award-number":["405786\/2022-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The arbovirus Chikungunya (CHIKV) is transmitted by Aedes mosquitoes in urban environments, and in humans, it triggers debilitating symptoms involving long-term complications, including arthritis and Guillain-Barr\u00e9 syndrome. The development of antiviral therapies is relevant, as no efficacious vaccine or drug has yet been approved for clinical application. As a detailed map of molecules underlying the viral infection can be obtained from the metabolome, we validated the metabolic signatures of Vero E6 cells prior to infection (CC), following CHIKV infection (CV) and also upon the inclusion of the nsP2 protease inhibitor wedelolactone (CWV), a coumestan which inhibits viral replication processes. The metabolome groups evidenced significant changes in the levels of lactate, myo-inositol, phosphocholine, glucose, betaine and a few specific amino acids. This study forms a preliminary basis for identifying metabolites through HR-MAS NMR (High Resolution Magic Angle Spinning Nuclear Magnetic Ressonance Spectroscopy) and proposing the affected metabolic pathways of cells following viral infection and upon incorporation of putative antiviral molecules.<\/jats:p>","DOI":"10.3390\/ijms25031414","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T04:35:40Z","timestamp":1706070940000},"page":"1414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["HR-MAS NMR Metabolomics Profile of Vero Cells under the Influence of Virus Infection and nsP2 Inhibitor: A Chikungunya Case Study"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5850-6360","authenticated-orcid":false,"given":"Rafaela dos S.","family":"Peinado","sequence":"first","affiliation":[{"name":"Multiuser Center for Biomolecular Innovation, Department of Physics, Institute of Biosciences, Languages and Exact Sciences (Ibilce\u2014UNESP), Sao Jose do Rio Preto, Sao Paulo 15054000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8266-5169","authenticated-orcid":false,"given":"Lucas G.","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), Campinas 13083862, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina C.","family":"Pacca","sequence":"additional","affiliation":[{"name":"Virology Research Laboratory, Medical School of Sao Jose do Rio Preto (FAMERP), Sao Paulo 15090000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7627-621X","authenticated-orcid":false,"given":"Marielena V.","family":"Saivish","sequence":"additional","affiliation":[{"name":"Virology Research Laboratory, Medical School of Sao Jose do Rio Preto (FAMERP), Sao Paulo 15090000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0453-6016","authenticated-orcid":false,"given":"Kelly C.","family":"Borsatto","sequence":"additional","affiliation":[{"name":"Multiuser Center for Biomolecular Innovation, Department of Physics, Institute of Biosciences, Languages and Exact Sciences (Ibilce\u2014UNESP), Sao Jose do Rio Preto, Sao Paulo 15054000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1102-2419","authenticated-orcid":false,"given":"Maur\u00edcio L.","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Virology Research Laboratory, Medical School of Sao Jose do Rio Preto (FAMERP), Sao Paulo 15090000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-7332","authenticated-orcid":false,"given":"Ljubica","family":"Tasic","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), Campinas 13083862, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2460-1145","authenticated-orcid":false,"given":"Raghuvir K.","family":"Arni","sequence":"additional","affiliation":[{"name":"Multiuser Center for Biomolecular Innovation, Department of Physics, Institute of Biosciences, Languages and Exact Sciences (Ibilce\u2014UNESP), Sao Jose do Rio Preto, Sao Paulo 15054000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8763-3884","authenticated-orcid":false,"given":"Raphael J.","family":"Eberle","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing IBI-7: Structural Biochemistry, Forschungszentrum J\u00fclich, 52428 J\u00fclich, Germany"},{"name":"Institut f\u00fcr Physikalische Biologie, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6518-6497","authenticated-orcid":false,"given":"M\u00f4nika A.","family":"Coronado","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing IBI-7: Structural Biochemistry, Forschungszentrum J\u00fclich, 52428 J\u00fclich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bellone, R., and Failloux, A.B. (2020). The Role of Temperature in Shaping Mosquito-Borne Viruses Transmission. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.584846"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-981-10-8727-1_1","article-title":"Arboviruses: A Family on the Move","volume":"1062","author":"Young","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e137","DOI":"10.1016\/S2666-5247(23)00029-0","article-title":"Neglected Tropical Diseases: Progress and Expectations","volume":"4","year":"2023","journal-title":"Lancet Microbe"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.actatropica.2016.11.020","article-title":"The Emergence of Arthropod-Borne Viral Diseases: A Global Prospective on Dengue, Chikungunya and Zika Fevers","volume":"166","author":"Mayer","year":"2017","journal-title":"Acta Trop."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1038\/nature06536","article-title":"Global Trends in Emerging Infectious Diseases","volume":"451","author":"Jones","year":"2008","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.idc.2019.08.006","article-title":"Chikungunya: Epidemiology, Pathogenesis, Clinical Features, Management, and Prevention","volume":"33","author":"Vairo","year":"2019","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.3390\/v7072792","article-title":"Early Events in Chikungunya Virus Infection\u2014From Virus Cell Binding to Membrane Fusion","volume":"7","author":"Hoornweg","year":"2015","journal-title":"Viruses"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e107","DOI":"10.1016\/S1473-3099(16)30385-1","article-title":"Chikungunya Virus: An Update on the Biology and Pathogenesis of This Emerging Pathogen","volume":"17","author":"Burt","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1080\/07391102.2020.1731602","article-title":"Discovery of Small Molecule Inhibitors of Chikungunya Virus Proteins (NsP2 and E1) Using in Silico Approaches","volume":"39","author":"Khan","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1128\/mr.58.3.491-562.1994","article-title":"The Alphaviruses: Gene Expression, Replication, and Evolution","volume":"58","author":"Strauss","year":"1994","journal-title":"Microbiol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/art.38221","article-title":"Effectiveness of Chloroquine and Inflammatory Cytokine Response in Patients With Early Persistent Musculoskeletal Pain and Arthritis Following Chikungunya Virus Infection","volume":"66","author":"Chopra","year":"2014","journal-title":"Arthritis Rheymatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.antiviral.2003.09.005","article-title":"In Vitro Inhibition of Chikungunya and Semliki Forest Viruses Replication by Antiviral Compounds: Synergistic Effect of Interferon-\u03b1 and Ribavirin Combination","volume":"61","author":"Briolant","year":"2004","journal-title":"Antivir. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1093\/jac\/dku209","article-title":"Mutations in the Chikungunya Virus Non-Structural Proteins Cause Resistance to Favipiravir (T-705), a Broad-Spectrum Antiviral","volume":"69","author":"Pastorino","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.4049\/jimmunol.1003139","article-title":"Chikungunya Virus Envelope-Specific Human Monoclonal Antibodies with Broad Neutralization Potency","volume":"186","author":"Warter","year":"2011","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1080\/17460441.2019.1629413","article-title":"Chikungunya Virus Drug Discovery: Still a Long Way to Go?","volume":"14","author":"Delang","year":"2019","journal-title":"Expert. Opin. Drug Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"ftv119","DOI":"10.1093\/femspd\/ftv119","article-title":"Chikungunya Virus: Recent Advances in Epidemiology, Host Pathogen Interaction & Vaccine Strategies","volume":"74","author":"Deeba","year":"2016","journal-title":"Pathog. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.arabjc.2017.03.008","article-title":"Effect and Mechanism of Wedelolactone as Antioxidant-Coumestan on OH-Treated Mesenchymal Stem Cells","volume":"13","author":"Li","year":"2020","journal-title":"Arab. J. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Yuan, F., Chen, J., Sun, P., Guan, S., and Xu, J. (2013). Wedelolactone Inhibits LPS-Induced pro-Inflammation via NF-KappaB Pathway. J. Biomed. Sci., 20.","DOI":"10.1186\/1423-0127-20-84"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/sj.cdd.4401325","article-title":"Wedelolactone Suppresses LPS-Induced Caspase-11 Expression by Directly Inhibiting the IKK Complex","volume":"11","author":"Kobori","year":"2004","journal-title":"Cell Death Differ."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e12868","DOI":"10.1111\/cpr.12868","article-title":"Wedelolactone Facilitates Ser\/Thr Phosphorylation of NLRP3 Dependent on PKA Signalling to Block Inflammasome Activation and Pyroptosis","volume":"53","author":"Pan","year":"2020","journal-title":"Cell Prolif."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhu, M.-M., Wang, L., Yang, D., Li, C., Pang, S.-T., Li, X.-H., Li, R., Yang, B., Lian, Y.P., and Ma, L. (2019). Wedelolactone Alleviates Doxorubicin-Induced Inflammation and Oxidative Stress Damage of Podocytes by I\u03baK\/I\u03baB\/NF\u03baB Pathway. Biomed. Pharmacother., 117.","DOI":"10.1016\/j.biopha.2019.109088"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1142\/S0192415X1850043X","article-title":"Hepatoprotective Effect of Wedelolactone against Concanavalin A-Induced Liver Injury in Mice","volume":"46","author":"Qingqiong","year":"2018","journal-title":"Am. J. Chin. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ejphar.2013.06.012","article-title":"Wedelolactone Exhibits Anti- Fi Brotic Effects on Human Hepatic Stellate","volume":"714","author":"Xia","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Peng, L., Yang, L., Xu, X., Li, W., and Luo, X. (2015). Wedelolactone Regulates Lipid Metabolism and Improves Hepatic Steatosis Partly by AMPK Activation and Up-Regulation of Expression of PPAR \u03b1\/LPL and LDLR. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132720"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"555","DOI":"10.3892\/ijo.2014.2769","article-title":"Wedelolactone Inhibits Breast Cancer-Induced Osteoclastogenesis by Decreasing Akt\/MTOR Signaling","volume":"46","author":"Hsieh","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jsbmb.2015.04.019","article-title":"Wedelolactone Induces Growth of Breast Cancer Cells by Stimulation of Estrogen Receptor Signalling","volume":"152","author":"Nehybova","year":"2015","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1158\/1535-7163.MCT-15-0861","article-title":"Wedelolactone, an Anti-Inflammatory Botanical, Interrupts c-Myc Oncogenic Signaling and Synergizes with Enzalutamide to Induce Apoptosis in Prostate Cancer Cells","volume":"15","author":"Sarveswaran","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.canlet.2011.01.002","article-title":"Inhibition of Topoisomerase II a: Novel Function of Wedelolactone","volume":"303","author":"Benes","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13049","DOI":"10.18632\/oncotarget.3790","article-title":"Wedelolactone Disrupts the Interaction of EZH2-EED Complex and Inhibits PRC2-Dependent Cancer","volume":"6","author":"Chen","year":"2015","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.3892\/ijo.2012.1664","article-title":"Wedelolactone, a Medicinal Plant-Derived Coumestan, Induces Caspase-Dependent Apoptosis in Prostate Cancer Cells via Downregulation of PKC \u03b5 without Inhibiting Akt","volume":"41","author":"Sarveswaran","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1002\/ptr.2252","article-title":"HIV-1 Protease and HIV-1 Integrase Inhibitory Substances from Eclipta Prostrata","volume":"21","author":"Tewtrakul","year":"2007","journal-title":"Phytother. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.jep.2012.09.036","article-title":"Identification and Evaluation of Anti Hepatitis C Virus Phytochemicals from Eclipta Alba","volume":"144","author":"Manvar","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.antiviral.2019.104677","article-title":"Wedelolactone Inhibits Human Cytomegalovirus Replication by Targeting Distinct Steps of the Viral Replication Cycle","volume":"174","author":"Svrlanska","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Emwas, A.H., Roy, R., McKay, R.T., Tenori, L., Saccenti, E., Gowda, G.A.N., Raftery, D., Alahmari, F., Jaremko, L., and Jaremko, M. (2019). NMR Spectroscopy for Metabolomics Research. Metabolites, 9.","DOI":"10.3390\/metabo9070123"},{"key":"ref_35","first-page":"124","article-title":"Metabolic Profiling of Cells in Response to Drug Treatment Using 1 H High-Resolution Magic Angle Spinning (HR-MAS) NMR Spectroscopy","volume":"71","author":"Vermathen","year":"2017","journal-title":"Bioorganomet. Chem. Mech."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Letertre, M.P.M., Giraudeau, P., and Tullio, P. (2021). De Nuclear Magnetic Resonance Spectroscopy in Clinical Metabolomics and Personalized Medicine: Current Challenges and Perspectives. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.698337"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/mrm.1910390302","article-title":"Gradient, High-Resolution, Magic Angle Spinning H Nuclear Magnetic Resonance Spectroscopy of Intact Cells","volume":"39","author":"Weybright","year":"1998","journal-title":"Magn. Reson. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Eberle, R.J., Olivier, D.S., Pacca, C.C., Avilla, C.M.S., Nogueira, M.L., Amaral, M.S., Willbold, D., and Arni, R.K. (2021). In Vitro Study of Hesperetin and Hesperidin as Inhibitors of Zika and Chikungunya Virus Proteases. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0246319"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5786","DOI":"10.1021\/acsomega.0c06191","article-title":"1,3-Thiazolbenzamide Derivatives as Chikungunya Virus NsP2 Protease Inhibitors","volume":"6","author":"Ivanova","year":"2021","journal-title":"ACS Omega"},{"key":"ref_40","first-page":"469","article-title":"Analysis of Cell Viability by the MTT Assay","volume":"2018","author":"Kumar","year":"2018","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1080\/10717544.2019.1582730","article-title":"Improving Cellular Uptake of Therapeutic Entities through Interaction with Components of Cell Membrane","volume":"26","author":"Zhang","year":"2019","journal-title":"Drug Deliv."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1023\/B:MCBI.0000049154.17866.00","article-title":"Da Mayaro Virus Infection Alters Glucose Metabolism in Cultured Cells through Activation of the Enzyme 6-Phosphofructo 1-Kinase","volume":"266","author":"Menezes","year":"2004","journal-title":"Mol. Cell. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.cmet.2018.03.008","article-title":"The Science and Translation of Lactate Shuttle Theory","volume":"27","author":"Brooks","year":"2018","journal-title":"Cell Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.tibtech.2010.06.005","article-title":"Glucose Metabolism in Mammalian Cell Culture: New Insights for Tweaking Vintage Pathways","volume":"28","author":"Mulukutla","year":"2010","journal-title":"Trends Biotechnol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"201","DOI":"10.4149\/av_2020_210","article-title":"Metabolic Reprogramming as a Feast for Virus Replication","volume":"64","author":"Polcicova","year":"2020","journal-title":"Acta Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/onc.2009.358","article-title":"Q\u2019s next: The Diverse Functions of Glutamine in Metabolism, Cell Biology and Cancer","volume":"29","author":"Deberardinis","year":"2010","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sa, F.J., Ange, C., and Rodr, M. (2021). The Role of Tricarboxylic Acid Cycle Metabolites in Viral Infections. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.725043"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cbf.1003","article-title":"Glutamine and Glutamate\u2014Their Central Role in Cell Metabolism and Function","volume":"21","author":"Newsholme","year":"2003","journal-title":"Cell Biochem. Funct."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1099\/jgv.0.000226","article-title":"Semliki Forest Virus and Sindbis Virus, but Not Vaccinia Virus, Require Glycolysis for Optimal Replication","volume":"96","author":"Findlay","year":"2015","journal-title":"J. General. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1126\/science.130.3373.432","article-title":"Amino Acid Metabolism Cell Cultures in Mammalian","volume":"130","author":"Eagle","year":"1955","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Bastin, G., Chotteau, V., and Wouwer, A. (2021). Vande Metabolic Flux Analysis of VERO Cells under Various Culture Conditions. Processes, 9.","DOI":"10.3390\/pr9122097"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Thaker, S.K., Ch, J., and Christofk, H.R. (2019). Viral Hijacking of Cellular Metabolism. BMC Biol., 17.","DOI":"10.1186\/s12915-019-0678-9"},{"key":"ref_53","unstructured":"Nelson, D.L., and Cox, M.M. (2017). Lehninger Principles of Biochemistry, W.H. Freeman. [7th ed.]."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev.nu.06.070186.003023","article-title":"Metabolism and Function of Myo-Inositol and Inositol Phospholipds","volume":"6","author":"Holub","year":"1986","journal-title":"Annu. Rev. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6747","DOI":"10.3390\/ijms23126747","article-title":"The Inositol Phosphate System\u2014A Coordinator of Metabolic Adaptability","volume":"23","author":"Kim","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Zhang, Z., He, G., Filipowicz, N.A., Randall, G., Belov, G.A., Kopek, B.G., and Wang, X. (2019). Host Lipids in Positive-Strand RNA Virus Genome Replication. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.00286"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.mib.2012.05.013","article-title":"Lipids at the Interface of Virus-Host Interactions","volume":"15","author":"Chukkapalli","year":"2013","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/tra.12230","article-title":"Phospholipid Synthesis and Transport in Mammalian Cells","volume":"16","author":"Vance","year":"2015","journal-title":"Traffic"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1194\/jlr.R700019-JLR200","article-title":"Phosphatidylcholine and Choline Homeostasis","volume":"49","author":"Li","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Perera, R., Riley, C., Isaac, G., Hopf-Jannasch, A.S., Moore, R.J., Weitz, K.W., Pasa-Tolic, L., Metz, T.O., Adamec, J., and Kuhn, R.J. (2012). Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002584"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/S0021-9258(19)86142-2","article-title":"Poliovirus Increases Phosphatidylcholine Biosynthesis in HeLa Cells by Stimulation of the Rate-Limiting Reaction Catalyzed by CTP: Phosphocholine cytidylyltransferase","volume":"255","author":"Vance","year":"1980","journal-title":"J. Biol. Chem."},{"key":"ref_62","first-page":"E1064","article-title":"Positive-Strand RNA Viruses Stimulate Host Phosphatidylcholine Synthesis at Viral Replication Sites","volume":"113","author":"Zhang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"155614","DOI":"10.1016\/j.metabol.2023.155614","article-title":"Roles of Malate and Aspartate in Gluconeogenesis in Various Physiological and Pathological States","volume":"145","year":"2023","journal-title":"Metabolism"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1021\/pr100892r","article-title":"Metabolomic Analysis of Livers and Serum from High-Fat Diet Induced Obese Mice","volume":"10","author":"Kim","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/ajcn\/80.3.539","article-title":"Betaine in Human Nutrition","volume":"80","author":"Craig","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7921","DOI":"10.1021\/acs.jafc.6b03592","article-title":"Antioxidant Mechanism of Betaine without Free Radical Scavenging Ability","volume":"64","author":"Zhang","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/0003-9861(72)90451-1","article-title":"Methionine Metabolism in Mammals: Kinetic Study of Betaine-Homocysteine Methyltransferase","volume":"153","author":"Harris","year":"1972","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Lauinger, L., and Kaiser, P. (2021). Sensing and Signaling of Methionine Metabolism. Metabolites, 11.","DOI":"10.3390\/metabo11020083"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.4161\/auto.20751","article-title":"Chikungunya-Induced Cell Death Is Limited by ER and Oxidative Stress-Induced Autophagy","volume":"8","author":"Joubert","year":"2012","journal-title":"Autophagy"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4849","DOI":"10.1002\/jsfa.9757","article-title":"L-Methionine Activates Nrf2-ARE Pathway to Induce Endogenous Antioxidant Activity for Depressing ROS-Derived Oxidative Stress in Growing Rats","volume":"99","author":"Wang","year":"2019","journal-title":"J. Sci. Food Agric."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1091\/mbc.E18-08-0515","article-title":"Methionine Coordinates a Hierarchically Organized Anabolic Program Enabling Proliferation","volume":"29","author":"Walvekar","year":"2018","journal-title":"Mol. Biol. Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s12035-020-02080-4","article-title":"Wedelolactone Mitigates Parkinsonism Via Alleviating Oxidative Stress and Mitochondrial Dysfunction Through NRF2\/SKN-1","volume":"58","author":"Sharma","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1152\/physrev.2000.80.3.1107","article-title":"Creatine and Creatinine Metabolism","volume":"80","author":"Wyss","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Bonilla, D.A., Kreider, R.B., Stout, J.R., Forero, D.A., Kerksick, C.M., Roberts, M.D., and Rawson, E.S. (2021). Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review. Nutrients, 13.","DOI":"10.3390\/nu13041238"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5137","DOI":"10.1128\/JVI.02179-08","article-title":"Involvement of Creatine Kinase B in Hepatitis C Virus Genome Replication through Interaction with the Viral NS4A Protein","volume":"83","author":"Hara","year":"2009","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1146\/annurev.nutr.27.061406.093621","article-title":"Creatine: Endogenous Metabolite, Dietary, and Therapeutic Supplement","volume":"27","author":"Brosnan","year":"2007","journal-title":"Annu. Rev. Nutr."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Eberle, R.J., Olivier, D.S., Amaral, M.S., Pacca, C.C., Nogueira, M.L., Arni, R.K., Willbold, D., and Coronado, M.A. (2022). Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteases. Microorganisms, 10.","DOI":"10.3390\/microorganisms10071331"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Nunes, M.R.T., Faria, N.R., de Vasconcelos, J.M., Golding, N., Kraemer, M.U.G., de Oliveira, L.F., da Silva Azevedo, R.d.S., da Silva, D.E.A., da Silva, E.V.P., and da Silva, S.P. (2015). Emergence and Potential for Spread of Chikungunya Virus in Brazil. BMC Med., 13.","DOI":"10.1186\/s12916-015-0348-x"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1093\/nar\/gkl923","article-title":"HMDB: The Human Metabolome Database","volume":"35","author":"Wishart","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1093\/nar\/gkm957","article-title":"BioMagResBank","volume":"36","author":"Ulrich","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: Narrowing the Gap between Raw Spectra and Functional Insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1007\/s11306-015-0823-6","article-title":"Computational and Statistical Analysis of Metabolomics Data","volume":"11","author":"Ren","year":"2015","journal-title":"Metabolomics"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/cem.785","article-title":"Partial Least Squares for Discrimination","volume":"17","author":"Barker","year":"2003","journal-title":"J. Chemom."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.chroma.2007.05.024","article-title":"Supervised Pattern Recognition in Food Analysis","volume":"1158","author":"Berrueta","year":"2007","journal-title":"J. Chromatogr. A"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:48:23Z","timestamp":1760104103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,24]]},"references-count":85,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25031414"],"URL":"https:\/\/doi.org\/10.3390\/ijms25031414","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,24]]}}}