{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:14:53Z","timestamp":1790252093300,"version":"4.1.0"},"reference-count":73,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Stazione Zoologica Anton Dohrn","award":["PG\/2018\/0494374"],"award-info":[{"award-number":["PG\/2018\/0494374"]}]},{"name":"Stazione Zoologica Anton Dohrn","award":["COVID-2020-12371849"],"award-info":[{"award-number":["COVID-2020-12371849"]}]},{"DOI":"10.13039\/501100003852","name":"\u201cAntitumor Drugs and Vaccines from the Sea (ADViSE)\u201d project","doi-asserted-by":"publisher","award":["PG\/2018\/0494374"],"award-info":[{"award-number":["PG\/2018\/0494374"]}],"id":[{"id":"10.13039\/501100003852","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003852","name":"\u201cAntitumor Drugs and Vaccines from the Sea (ADViSE)\u201d project","doi-asserted-by":"publisher","award":["COVID-2020-12371849"],"award-info":[{"award-number":["COVID-2020-12371849"]}],"id":[{"id":"10.13039\/501100003852","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PG\/2018\/0494374"],"award-info":[{"award-number":["PG\/2018\/0494374"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["COVID-2020-12371849"],"award-info":[{"award-number":["COVID-2020-12371849"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Italian Ministry of Health Ricerca Corrente\u2014IRCCS MultiMedic","award":["PG\/2018\/0494374"],"award-info":[{"award-number":["PG\/2018\/0494374"]}]},{"name":"Italian Ministry of Health Ricerca Corrente\u2014IRCCS MultiMedic","award":["COVID-2020-12371849"],"award-info":[{"award-number":["COVID-2020-12371849"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Contact between SARS-CoV-2 and human lung cells involves the viral spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor on epithelial cells, the latter being strongly involved in the regulation of inflammation as well as blood pressure homeostasis. SARS-CoV-2 infection is characterized by a strong inflammatory response defined as a \u201ccytokine storm\u201d. Among recent therapeutic approaches against SARS-CoV-2 targeting the dramatic inflammatory reaction, some natural products are promising. Diatoms are microalgae able to produce bioactive secondary metabolites, such as the xanthophyll diatoxanthin (Dt). The aim of this study is to demonstrate the anti-inflammatory effects of Dt on the A549-hACE2 lung cell line, exploring its interaction with the ACE2 receptor, as well as depicting its role in inhibiting a cytokine storm induced by the SARS-CoV-2 spike glycoprotein. Results showed that Dt enhanced the cell metabolism, e.g., the percent of metabolically active cells, as well as the ACE2 enzymatic activity. Moreover, Dt strongly affected the response of the SARS-CoV-2 spike glycoprotein-exposed A549-hACE2 cells in decreasing the interleukin-6 production and increasing the interleukin-10 release. Moreover, Dt upregulated genes encoding for the interferon pathway related to antiviral defense and enhanced proteins belonging to the innate immunity response. The potential interest of Dt as a new therapeutic agent in the treatment and\/or prevention of the severe inflammatory syndrome related to SARS-CoV-2 infection is postulated.<\/jats:p>","DOI":"10.3390\/antiox11081515","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T20:52:01Z","timestamp":1659559921000},"page":"1515","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung Cells"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3007-8154","authenticated-orcid":false,"given":"Clementina","family":"Sansone","sequence":"first","affiliation":[{"name":"Stazione Zoologica Anton Dohrn, sede Molosiglio Marina Acton, Via Ammiraglio F. Acton 55, 80133 Napoli, Italy"},{"name":"Institute of Biomolecular Chemistry, CNR, Via Campi Flegrei 34, Pozzuoli, 80078 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2638-2935","authenticated-orcid":false,"given":"Luigi","family":"Pistelli","sequence":"additional","affiliation":[{"name":"Stazione Zoologica Anton Dohrn, sede Molosiglio Marina Acton, Via Ammiraglio F. Acton 55, 80133 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7983-0861","authenticated-orcid":false,"given":"Angelo","family":"Del Mondo","sequence":"additional","affiliation":[{"name":"Stazione Zoologica Anton Dohrn, sede Molosiglio Marina Acton, Via Ammiraglio F. Acton 55, 80133 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Calabrone","sequence":"additional","affiliation":[{"name":"Stazione Zoologica Anton Dohrn, sede Molosiglio Marina Acton, Via Ammiraglio F. Acton 55, 80133 Napoli, Italy"},{"name":"Unit of Molecular Pathology, Biochemistry and Immunology, IRCCS MultiMedica, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5453-461X","authenticated-orcid":false,"given":"Angelo","family":"Fontana","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry, CNR, Via Campi Flegrei 34, Pozzuoli, 80078 Napoli, Italy"},{"name":"Department of Biology, University of Naples \u201cFederico II\u201d, Via Cupa Nuova Cinthia 21, 80126 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8058-0719","authenticated-orcid":false,"given":"Douglas M.","family":"Noonan","sequence":"additional","affiliation":[{"name":"Unit of Molecular Pathology, Biochemistry and Immunology, IRCCS MultiMedica, 20138 Milan, Italy"},{"name":"Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9624-5103","authenticated-orcid":false,"given":"Adriana","family":"Albini","sequence":"additional","affiliation":[{"name":"IRCCS European Institute of Oncology, IEO, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Brunet","sequence":"additional","affiliation":[{"name":"Stazione Zoologica Anton Dohrn, sede Molosiglio Marina Acton, Via Ammiraglio F. Acton 55, 80133 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fuentes-Prior, P. (2021). Priming of SARS-CoV-2 S protein by several membrane-bound serine proteinases could explain enhanced viral infectivity and systemic COVID-19 infection. J. Biol. Chem., 296.","DOI":"10.1074\/jbc.REV120.015980"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tang, L., Yin, Z., Hu, Y., and Mei, H. (2020). Controlling Cytokine Storm Is Vital in COVID-19. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.570993"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hsu, R.J., Yu, W.C., Peng, G.R., Ye, C.H., Hu, S., Chong, P.C.T., Yap, K.Y., Lee, J.Y.C., Lin, W.C., and Yu, S.H. (2022). The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections. Front. 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