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Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","award":["0641\/2020-88881.507175\/2020-01"],"award-info":[{"award-number":["0641\/2020-88881.507175\/2020-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Exacerbated inflammatory responses are a hallmark of severe coronavirus disease 2019 (COVID-19). Zileuton (Zi) is a selective inhibitor of 5-lipoxygenase, an enzyme involved in the production of several inflammatory\/pro-resolving lipid mediators. Herein, we investigated the effect of Zi treatment in a severe acute respiratory syndrome (SARS) model. Mouse hepatitis virus (MHV)3-infected mice treated with Zi significantly improved the clinical score, weight loss, cardiopulmonary function, and survival rates compared with infected untreated animals. The protection observed in Zi-treated mice was associated with a lower inflammatory score, reduced dendritic cell-producing tumor necrosis factor (TNF), and increased neutrophil-producing interleukin (IL)-10 in the lungs three days after infection (dpi). At 5 dpi, the lungs of treated mice showed an increase in Th2-, Treg CD4+-, and Treg CD8+-producing IL-10 and reduced Th1 infiltrating cells. Furthermore, similar results were found upon Zi treatment after SARS-CoV-2 infection in transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2), significantly improving the clinical score, weight loss, and lung inflammatory score compared with untreated animals. Our data suggest that Zi protects against developing severe lung disease during SARS induced by betacoronavirus without affecting the host\u2019s capacity to deal with infection.<\/jats:p>","DOI":"10.3390\/v15102049","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T07:47:52Z","timestamp":1696405672000},"page":"2049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A 5-Lipoxygenase Inhibitor, Zileuton, Modulates Host Immune Responses and Improves Lung Function in a Model of Severe Acute Respiratory Syndrome (SARS) Induced by Betacoronavirus"],"prefix":"10.3390","volume":"15","author":[{"given":"Rafaela das Dores","family":"Pereira","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayane Aparecida Nonato","family":"Rabelo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia Fernanda de Melo","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Luiz Teixeira","family":"Porto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9724-4164","authenticated-orcid":false,"given":"Ana Claudia dos Santos Pereira","family":"Andrade","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso M.","family":"Queiroz-Junior","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar Lu\u00eds Nascimento","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"},{"name":"Program in Health Sciences: Infectious Diseases and Tropical Medicine, Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3897-7872","authenticated-orcid":false,"given":"Luiz Pedro","family":"de Souza-Costa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8392-1467","authenticated-orcid":false,"given":"Felipe Rocha da Silva","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Bento Rodrigues","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara Lu\u00edsa Vieira","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna L.","family":"Umezu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, 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F.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1365-2318","authenticated-orcid":false,"given":"Jader Santos","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"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 Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian Vasconcelos","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana Sim\u00e3o","family":"Machado","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"},{"name":"Program in Health Sciences: Infectious Diseases and Tropical Medicine, Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1001\/jamainternmed.2020.0994","article-title":"Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China","volume":"180","author":"Wu","year":"2020","journal-title":"JAMA Intern. 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