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This study evaluated the antiviral activity of biflavanones isolated from <jats:italic>Ouratea spectabilis<\/jats:italic>\u2014specifically ouratein (Our\u2010) A, B, C, and D\u2014against murine hepatitis virus (MHV\u20103) and human SARS\u2010CoV\u20102. Cells infected with MHV\u20103 or SARS\u2010CoV\u20102 were treated with ourateins, and viral replication was assessed using plaque assays. Mice infected with MHV\u20103 were treated with Our\u2010D either orally or intraperitoneally. Key assessments included leukocyte counts, cytokine and chemokine levels, histological analysis, and survival rates. The mechanism of action was explored through <jats:italic>in silico<\/jats:italic> and in\u00a0vitro studies focused on the binding and inhibition of the main protease (M<jats:sup>pro<\/jats:sup>). Our\u2010D significantly inhibited the replication of both viruses, with a selective index of 2.5 for MHV\u20103 and 14.9 for SARS\u2010CoV\u20102. In\u00a0vivo, Our\u2010D reduced leukocyte infiltration in the lungs, decreased CCL2 levels, increased IL\u201010, and lowered plasma IL\u20106 and CXCL1 levels. Additionally, Our\u2010D mitigated lung damage, partially restored betacoronavirus\u2010induced lymphopenia, and reduced viral loads in the lungs, heart, and spleen, ultimately improving survival in mice. <jats:italic>In silico<\/jats:italic> studies revealed that Our\u2010A and Our\u2010C had strong binding affinity for M<jats:sup>pro<\/jats:sup>, and both significantly inhibited M<jats:sup>pro<\/jats:sup> activity in\u00a0vitro, unlike Our\u2010D. Our\u2010D protected mice from coronavirus infection by modulating the inflammatory response and reducing viral loads, with minimal effect on M<jats:sup>pro<\/jats:sup> inhibition, suggesting alternative mechanisms for its antiviral activity.<\/jats:p>","DOI":"10.1002\/ptr.8462","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T11:34:12Z","timestamp":1742297652000},"page":"2180-2196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ouratein D, a Biflavanone From <i>Ouratea spectabilis<\/i>, Alleviates Betacoronavirus Infection by Mitigating Inflammation, Lung Damage and Viral Replication"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8334-1219","authenticated-orcid":false,"given":"Adelson H\u00e9ric A.","family":"Monteiro","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Products, Faculty of Pharmacy Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K\u00e1tia M.","family":"Freitas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Products, Faculty of Pharmacy Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Clara M.","family":"Montuori\u2010Andrade","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Products, Faculty of Pharmacy Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erick Bryan Sousa","family":"de Lima","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis and Toxicology, Faculty of Pharmacy Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ant\u00f4nio Felipe S.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis and Toxicology, Faculty of Pharmacy Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Products, Faculty of Pharmacy Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edvaldo S.","family":"Lara","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis and Toxicology, Faculty of Pharmacy Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo Camilo","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Zaidan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Products, Faculty of Pharmacy Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe Rocha Silva","family":"da Santos","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biological Sciences Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filipe","family":"Resende","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biological Sciences Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz Pedro","family":"Souza\u2010Costa","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biological Sciences Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celso M.","family":"Queiroz\u2010Junior","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biological Sciences Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian de Meira","family":"Chaves","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biological Sciences Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nat\u00e1lia R. 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