Ouratein D, a Biflavanone From <i>Ouratea spectabilis</i>, Alleviates Betacoronavirus Infection by Mitigating Inflammation, Lung Damage and Viral Replication

Severe coronavirus outbreaks, including SARS, MERS, and COVID-19, have underscored the urgent need for effective antiviral therapies. This study evaluated the antiviral activity of biflavanones isolated from Ouratea spectabilis-specifically ouratein (Our-) A, B, C, and D-against murine hepatitis virus (MHV-3) and human SARS-CoV-2. Cells infected with MHV-3 or SARS-CoV-2 were treated with ourateins, and viral replication was assessed using plaque assays. Mice infected with MHV-3 were treated with Our-D 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 in silico and in vitro studies focused on the binding and inhibition of the main protease (M<sup>pro</sup>). Our-D significantly inhibited the replication of both viruses, with a selective index of 2.5 for MHV-3 and 14.9 for SARS-CoV-2. In vivo, Our-D reduced leukocyte infiltration in the lungs, decreased CCL2 levels, increased IL-10, and lowered plasma IL-6 and CXCL1 levels. Additionally, Our-D mitigated lung damage, partially restored betacoronavirus-induced lymphopenia, and reduced viral loads in the lungs, heart, and spleen, ultimately improving survival in mice. In silico studies revealed that Our-A and Our-C had strong binding affinity for M<sup>pro</sup>, and both significantly inhibited M<sup>pro</sup> activity in vitro, unlike Our-D. Our-D protected mice from coronavirus infection by modulating the inflammatory response and reducing viral loads, with minimal effect on M<sup>pro</sup> inhibition, suggesting alternative mechanisms for its antiviral activity.

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Publication Details

Journal
Phytotherapy Research
Published
2025-03-18
DOI
https://doi.org/10.1002/ptr.8462
Primary Topic
Pneumocystis jirovecii pneumonia detection and treatment
Type
article
Field-Weighted Citation Impact
0.00

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article

Ouratein D, a Biflavanone From Ouratea spectabilis, Alleviates Betacoronavirus Infection by Mitigating Inflammation, Lung Damage and Viral Replication

Mariana Ortiz de Godoy, Marina Pereira Rocha, Kátia Michelle Freitas, Natália Ribeiro Cabacinha Nóbrega et al.
Phytotherapy Research
Pneumocystis jirovecii pneumonia detection and treatment
article

Ouratein D, a Biflavanone From Ouratea spectabilis, Alleviates Betacoronavirus Infection by Mitigating Inflammation, Lung Damage and Viral Replication

Mariana Ortiz de Godoy, Marina Pereira Rocha, Kátia Michelle Freitas, Natália Ribeiro Cabacinha Nóbrega, Isabella Zaidan, Lirlândia P. Sousa, Celso Martins Queiroz‐Junior, Mauro Martins Teixeira, Rodrigo Maia de Pádua, Fernão Castro Braga, Vinícius Gonçalves Maltarollo, Evellyn Thauany Alves de Lima, A. Monteiro, Glaucius Oliva, Ian de Meira Chaves, Luiza Valença Barreto, Rafaela Salgado Ferreira, Leonardo Camilo de Oliveira, Camila Cardoso, Luiz Pedro Souza‐Costa, Filipe Resende, Antônio Felipe Silva Carvalho, Márcio Dias Rabelo, Rafael V. C. Guido, Ana Clara M. Montuori‐Andrade, Priscilla Rodrigues Valadares Campana, Thales Kronenberger, Vivian Vasconcelos Costa, Felipe Rocha da Silva Santos, Edvaldo S. Lara
article en

Abstract

Severe coronavirus outbreaks, including SARS, MERS, and COVID-19, have underscored the urgent need for effective antiviral therapies. This study evaluated the antiviral activity of biflavanones isolated from Ouratea spectabilis-specifically ouratein (Our-) A, B, C, and D-against murine hepatitis virus (MHV-3) and human SARS-CoV-2. Cells infected with MHV-3 or SARS-CoV-2 were treated with ourateins, and viral replication was assessed using plaque assays. Mice infected with MHV-3 were treated with Our-D 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 in silico and in vitro studies focused on the binding and inhibition of the main protease (M<sup>pro</sup>). Our-D significantly inhibited the replication of both viruses, with a selective index of 2.5 for MHV-3 and 14.9 for SARS-CoV-2. In vivo, Our-D reduced leukocyte infiltration in the lungs, decreased CCL2 levels, increased IL-10, and lowered plasma IL-6 and CXCL1 levels. Additionally, Our-D mitigated lung damage, partially restored betacoronavirus-induced lymphopenia, and reduced viral loads in the lungs, heart, and spleen, ultimately improving survival in mice. In silico studies revealed that Our-A and Our-C had strong binding affinity for M<sup>pro</sup>, and both significantly inhibited M<sup>pro</sup> activity in vitro, unlike Our-D. Our-D protected mice from coronavirus infection by modulating the inflammatory response and reducing viral loads, with minimal effect on M<sup>pro</sup> inhibition, suggesting alternative mechanisms for its antiviral activity.

Phytotherapy ResearchVol. 39(5)
Universidade Federal de Minas Gerais (BR), University of Eastern Finland (FI), Universidade de São Paulo (BR), German Center for Infection Research (DE)
Deutsches Zentrum für Infektionsforschung, Fundação de Amparo à Pesquisa do Estado de São Paulo, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Bundesministerium für Bildung und Forschung, Conselho Nacional de Desenvolvimento Científico e Tecnológico
Good health and well-being
Openalex Percentile: Top 92%
Pneumocystis jirovecii pneumonia detection and treatment
DOIOpen Access PDFOpenAlex
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