{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:11:01Z","timestamp":1782274261225,"version":"3.54.5"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T00:00:00Z","timestamp":1681776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANPCYT","award":["PICT N\u00b0 2018-01588"],"award-info":[{"award-number":["PICT N\u00b0 2018-01588"]}]},{"name":"ANPCYT","award":["PIP N\u00b0 11220200102513CO"],"award-info":[{"award-number":["PIP N\u00b0 11220200102513CO"]}]},{"name":"CONICET","award":["PICT N\u00b0 2018-01588"],"award-info":[{"award-number":["PICT N\u00b0 2018-01588"]}]},{"name":"CONICET","award":["PIP N\u00b0 11220200102513CO"],"award-info":[{"award-number":["PIP N\u00b0 11220200102513CO"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>New antiviral treatments are needed to deal with the unpredictable emergence of viruses. Furthermore, vaccines and antivirals are only available for just a few viral infections, and antiviral drug resistance is an increasing concern. Cyanidin (a natural product also called A18), a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, through its anti-inflammatory effects. Regarding its mechanism of action, A18 was identified as an IL-17A inhibitor, resulting in the attenuation of IL-17A signaling and associated diseases in mice. Importantly, A18 also inhibits the NF-\u03baB signaling pathway in different cell types and conditions in vitro and in vivo. In this study, we report that A18 restricts RSV, HSV-1, canine coronavirus, and SARS-CoV-2 multiplication, indicating a broad-spectrum antiviral activity. We also found that A18 can control cytokine and NF-\u03baB induction in RSV-infected cells independently of its antiviral activity. Furthermore, in mice infected with RSV, A18 not only significantly reduces viral titers in the lungs, but also diminishes lung injury. Thus, these results provide evidence that A18 could be used as a broad-spectrum antiviral and may contribute to the development of novel therapeutic targets to control these viral infections and pathogenesis.<\/jats:p>","DOI":"10.3390\/v15040989","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T02:30:03Z","timestamp":1681785003000},"page":"989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Flavonoid Cyanidin Shows Immunomodulatory and Broad-Spectrum Antiviral Properties, Including SARS-CoV-2"],"prefix":"10.3390","volume":"15","author":[{"given":"Josefina","family":"Vicente","sequence":"first","affiliation":[{"name":"Laboratorio de Virolog\u00eda, Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina"},{"name":"Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET\u2014Universidad de Buenos Aires, Buenos Aires 1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Benedetti","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda, Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5852-3359","authenticated-orcid":false,"given":"Paula","family":"Martelliti","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda, Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Unidad Operativa Centro de Contenci\u00f3n Biol\u00f3gica (UOCCB), Administraci\u00f3n Nacional de Laboratorios e Institutos de Salud (ANLIS), Buenos Aires 1282, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Virginia","family":"Gentilini","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Traslacional, Trasplante y Bioingenier\u00eda (IMETTYB)-CONICET, Buenos Aires 1093, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freddy Armando","family":"Pe\u00f1aranda Figueredo","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda, Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina"},{"name":"Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET\u2014Universidad de Buenos Aires, Buenos Aires 1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes Soledad","family":"Nabaes Jodar","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires 1425, Argentina"},{"name":"Laboratorio de Virolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires 1417, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6506-1635","authenticated-orcid":false,"given":"Mariana","family":"Viegas","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires 1425, Argentina"},{"name":"Laboratorio de Virolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires 1417, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3341-9719","authenticated-orcid":false,"given":"Andrea Alejandra","family":"Barquero","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda, Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina"},{"name":"Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET\u2014Universidad de Buenos Aires, Buenos Aires 1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0209-6870","authenticated-orcid":false,"given":"Carlos Alberto","family":"Bueno","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda, Departamento de Qu\u00edmica Biol\u00f3gica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina"},{"name":"Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET\u2014Universidad de Buenos Aires, Buenos Aires 1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1126\/science.abn1900","article-title":"Stopping pandemics before they start: Lessons learned from SARS-CoV-2","volume":"375","author":"Edwards","year":"2022","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8353","DOI":"10.3390\/molecules27238353","article-title":"Tackling the Future Pandemics: Broad-Spectrum Antiviral Agents (BSAAs) Based on A-Type Proanthocyanidins","volume":"27","author":"Maffei","year":"2022","journal-title":"Molecules"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.antiviral.2018.07.020","article-title":"Comparison of antiviral resistance across acute and chronic viral infections","volume":"158","author":"Mason","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.chembiol.2022.05.009","article-title":"Identifying enhancers of innate immune signaling as broad-spectrum antivirals active against emerging viruses","volume":"29","author":"Maarifi","year":"2022","journal-title":"Cell Chem. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"105278","DOI":"10.1016\/j.antiviral.2022.105278","article-title":"Novel antiviral activity of PAD inhibitors against human beta-coronaviruses HCoV-OC43 and SARS-CoV-2","volume":"200","author":"Pasquero","year":"2022","journal-title":"Antivir. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"871583","DOI":"10.3389\/fphar.2022.871583","article-title":"p53\/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics)","volume":"13","author":"Milani","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"549","DOI":"10.3389\/fimmu.2020.00549","article-title":"Herpes Simplex Virus 1 UL2 Inhibits the TNF-\u03b1-Mediated NF-\u03baB Activity by Interacting With p65\/p50","volume":"11","author":"Cai","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.3389\/fimmu.2020.01229","article-title":"Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in COVID-19: Key Therapeutic Targets?","volume":"11","author":"Sallenave","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00441-18","DOI":"10.1128\/JVI.00441-18","article-title":"Central role of the NF-\u03baB pathway in the scgb1a1-expressing epithelium in mediating respiratory syncytial virus-induced airway inflammation","volume":"92","author":"Tian","year":"2018","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6480","DOI":"10.1002\/fsn3.2554","article-title":"Anti-inflammatory activity of cyanidin-3-O-glucoside and cyanidin-3-O-glucoside liposomes in THP-1 macrophages","volume":"9","author":"Hao","year":"2021","journal-title":"Food Sci. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"995391","DOI":"10.3389\/fnut.2022.995391","article-title":"Cellular uptake, transport mechanism and anti-inflammatory effect of cyanidin-3-glucoside nanoliposomes in Caco-2\/RAW 264.7 co-culture model","volume":"9","author":"Yang","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1111\/1750-3841.16125","article-title":"Cyanidin-3-O-glucoside, cyanidin, and oxidation products of cyanidin protect neuronal function through alleviating inflammation and oxidative damage","volume":"87","author":"Zhu","year":"2022","journal-title":"J. Food Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1021\/acschemneuro.2c00087","article-title":"Cyanidin Chloride Improves LPS-Induced Depression-Like Behavior in Mice by Ameliorating Hippocampal Inflammation and Excitotoxicity","volume":"13","author":"Qu","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_14","first-page":"10","article-title":"The flavonoid cyanidin blocks binding of the cytokine interleukin-17A to the IL-17RA subunit to alleviate inflammation in vivo","volume":"21","author":"Liu","year":"2017","journal-title":"Sci. Signal."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wang, B., Cui, S., Mao, B., Zhang, Q., Tian, F., Zhao, J., Tang, X., and Chen, W. (2022). Cyanidin Alleviated CCl4-Induced Acute Liver Injury by Regulating the Nrf2 and NF-\u03baB Signaling Pathways. Antioxidants, 11.","DOI":"10.3390\/antiox11122383"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1038\/aps.2017.203","article-title":"Cyanidin attenuates A\u03b2 25-35-induced neuroinflammation by suppressing NF-\u03baB activity downstream of TLR4\/NOX4 in human neuroblastoma cells","volume":"39","author":"Thummayot","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1111\/jphp.13002","article-title":"Virucidal, antiviral and immunomodulatory activities of \u03b2-escin and Aesculus hippocastanum extract","volume":"70","author":"Michelini","year":"2018","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2019.01.018","article-title":"Aesculus hippocastanum L. seed extract shows virucidal and antiviral activities against respiratory syncytial virus (RSV) and reduces lung inflammation in vivo","volume":"164","author":"Salinas","year":"2019","journal-title":"Antiviral. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e00531","DOI":"10.1002\/prp2.531","article-title":"Azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model","volume":"29","author":"Zappia","year":"2019","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.3389\/fimmu.2019.02152","article-title":"Host Components Contributing to Respiratory Syncytial Virus Pathogenesis","volume":"10","author":"Carvajal","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104817","DOI":"10.1016\/j.antiviral.2020.104817","article-title":"Imiquimod suppresses respiratory syncytial virus (RSV) replication via PKA pathway and reduces RSV induced-inflammation and viral load in mice lungs","volume":"179","author":"Salinas","year":"2020","journal-title":"Antiviral. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"977","DOI":"10.2353\/ajpath.2006.051055","article-title":"Differential immune responses and pulmonary pathophysiology are induced by two different strains of respiratory syncytial virus","volume":"169","author":"Lukacs","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/978-1-4939-3687-8_15","article-title":"Mouse and cotton rat models of human respiratory syncytial virus","volume":"1442","author":"Rudd","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5782","DOI":"10.1128\/JVI.01693-10","article-title":"Differential pathogenesis of respiratory syncytial virus clinical isolates in BALB\/c mice","volume":"85","author":"Stokes","year":"2011","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Resch, B. (2011). Human Respiratory Syncytial Virus Infection, InTech.","DOI":"10.5772\/1496"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/S2213-2600(22)00213-2","article-title":"Early treatment to prevent progression of SARS-CoV-2 infection","volume":"10","author":"Cohen","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"D\u2019Abramo, A., Vita, S., and Nicastri, E. (2022). The unmet need for COVID-19 treatment in immunocompromised patients. BMC Infect. Dis., 22.","DOI":"10.1186\/s12879-022-07918-x"},{"key":"ref_28","unstructured":"(2023, March 15). Therapeutics and COVID-19: Living Guideline (v13.1). World Health Organization (WHO). Available online: https:\/\/app.magicapp.org\/#\/guideline\/6914."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1016\/S0140-6736(22)00478-0","article-title":"Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: A systematic an\u00e1lisis","volume":"399","author":"Li","year":"2022","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"220105","DOI":"10.1183\/16000617.0105-2022","article-title":"Burden of respiratory syncytial virus infection in older and high-risk adults: A systematic review and meta-analysis of the evidence from developed countries","volume":"31","author":"Martin","year":"2022","journal-title":"Eur. Respir. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Gatt, D., Martin, I., AlFouzan, R., and Moraes, T. (2023). Prevention and Treatment Strategies for Respiratory Syncytial Virus (RSV). Pathogens, 12.","DOI":"10.3390\/pathogens12020154"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Greenan, E., Gallagher, S., Khalil, R., Murphy, C.C., and N\u00ed Gabhann-Dromgoole, J. (2021). Advancing Our Understanding of Corneal Herpes Simplex Virus-1 Immune Evasion Mechanisms and Future Therapeutics. Viruses, 13.","DOI":"10.3390\/v13091856"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2606583","DOI":"10.1155\/2018\/2606583","article-title":"Antiviral Activities of Mulberry (Morus alba) Juice and Seed against Influenza Viruses","volume":"2018","author":"Kim","year":"2018","journal-title":"Evid Based Complement. Altern. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sivarajan, R., Oberwinkler, H., Roll, V., K\u00f6nig, E.M., Steinke, M., and Bodem, J. (2022). A defined anthocyanin mixture sourced from bilberry and black currant inhibits Measles virus and various herpesviruses. BMC Complement. Med. Ther., 22.","DOI":"10.1186\/s12906-022-03661-7"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.3389\/fmicb.2017.01314","article-title":"Antiviral Properties of the Natural Polyphenols Delphinidin and Epigallocatechin Gallate against the Flaviviruses West Nile Virus, Zika Virus, and Dengue Virus","volume":"8","author":"Saiz","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"21723","DOI":"10.1038\/s41598-022-26157-3","article-title":"In vitro screening of anti-viral and virucidal effects against SARS-CoV-2 by Hypericum perforatum and Echinacea","volume":"12","author":"Bajrai","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_37","first-page":"3742318","article-title":"Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein","volume":"2022","author":"Shrestha","year":"2022","journal-title":"Adv. Pharmacol. Pharm. Sci."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/4\/989\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:17:45Z","timestamp":1760123865000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/4\/989"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,18]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["v15040989"],"URL":"https:\/\/doi.org\/10.3390\/v15040989","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,18]]}}}