Ouratein D, a Biflavanone From Ouratea spectabilis, Alleviates Betacoronavirus Infection by Mitigating Inflammation, Lung Damage and Viral Replication
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Wiley
2025
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| author | Adelson Héric A. Monteiro Kátia M. Freitas Ana Clara M. Montuori‐Andrade Erick Bryan Sousa de Lima Antônio Felipe S. Carvalho Camila Cardoso Edvaldo S. Lara Leonardo Camilo Oliveira Isabella Zaidan Felipe Rocha Silva da Santos Filipe Resende Luiz Pedro Souza‐Costa Celso M. Queiroz‐Junior Ian de Meira Chaves Natália R. C. Nóbrega Maria Beatriz O. Rabelo Marina P. Rocha Priscilla R. V. Campana Rodrigo M. Pádua Rafaela S. Ferreira Luiza V. Barreto Thales Kronenberger Vinícius G. Maltarollo Mariana O. de Godoy Glaucius Oliva Rafael V. C. Guido Mauro M. Teixeira Vivian V. Costa Lirlândia P. Sousa Fernão C. Braga |
| author_facet | Adelson Héric A. Monteiro Kátia M. Freitas Ana Clara M. Montuori‐Andrade Erick Bryan Sousa de Lima Antônio Felipe S. Carvalho Camila Cardoso Edvaldo S. Lara Leonardo Camilo Oliveira Isabella Zaidan Felipe Rocha Silva da Santos Filipe Resende Luiz Pedro Souza‐Costa Celso M. Queiroz‐Junior Ian de Meira Chaves Natália R. C. Nóbrega Maria Beatriz O. Rabelo Marina P. Rocha Priscilla R. V. Campana Rodrigo M. Pádua Rafaela S. Ferreira Luiza V. Barreto Thales Kronenberger Vinícius G. Maltarollo Mariana O. de Godoy Glaucius Oliva Rafael V. C. Guido Mauro M. Teixeira Vivian V. Costa Lirlândia P. Sousa Fernão C. Braga Adelson Héric A. Monteiro Kátia M. Freitas Ana Clara M. Montuori‐Andrade Erick Bryan Sousa de Lima Antônio Felipe S. Carvalho Camila Cardoso Edvaldo S. Lara Leonardo Camilo Oliveira Isabella Zaidan Felipe Rocha Silva da Santos Filipe Resende Luiz Pedro Souza‐Costa Celso M. Queiroz‐Junior Ian de Meira Chaves Natália R. C. Nóbrega Maria Beatriz O. Rabelo Marina P. Rocha Priscilla R. V. Campana Rodrigo M. Pádua Rafaela S. Ferreira Luiza V. Barreto Thales Kronenberger Vinícius G. Maltarollo Mariana O. de Godoy Glaucius Oliva Rafael V. C. Guido Mauro M. Teixeira Vivian V. Costa Lirlândia P. Sousa Fernão C. Braga |
| collection | Wiley Open Access |
| contents | Ouratein D, a Biflavanone From Ouratea spectabilis, Alleviates Betacoronavirus Infection by Mitigating Inflammation, Lung Damage and Viral Replication Adelson Héric A. Monteiro Kátia M. Freitas Ana Clara M. Montuori‐Andrade Erick Bryan Sousa de Lima Antônio Felipe S. Carvalho Camila Cardoso Edvaldo S. Lara Leonardo Camilo Oliveira Isabella Zaidan Felipe Rocha Silva da Santos Filipe Resende Luiz Pedro Souza‐Costa Celso M. Queiroz‐Junior Ian de Meira Chaves Natália R. C. Nóbrega Maria Beatriz O. Rabelo Marina P. Rocha Priscilla R. V. Campana Rodrigo M. Pádua Rafaela S. Ferreira Luiza V. Barreto Thales Kronenberger Vinícius G. Maltarollo Mariana O. de Godoy Glaucius Oliva Rafael V. C. Guido Mauro M. Teixeira Vivian V. Costa Lirlândia P. Sousa Fernão C. Braga Phytotherapy Research ABSTRACTSevere 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 (Mpro). 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 Mpro, and both significantly inhibited Mpro 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 Mpro inhibition, suggesting alternative mechanisms for its antiviral activity. 10.1002/ptr.8462 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/ptr.8462 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_ptr_8462 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Ouratein D, a Biflavanone From Ouratea spectabilis, Alleviates Betacoronavirus Infection by Mitigating Inflammation, Lung Damage and Viral Replication Adelson Héric A. Monteiro Kátia M. Freitas Ana Clara M. Montuori‐Andrade Erick Bryan Sousa de Lima Antônio Felipe S. Carvalho Camila Cardoso Edvaldo S. Lara Leonardo Camilo Oliveira Isabella Zaidan Felipe Rocha Silva da Santos Filipe Resende Luiz Pedro Souza‐Costa Celso M. Queiroz‐Junior Ian de Meira Chaves Natália R. C. Nóbrega Maria Beatriz O. Rabelo Marina P. Rocha Priscilla R. V. Campana Rodrigo M. Pádua Rafaela S. Ferreira Luiza V. Barreto Thales Kronenberger Vinícius G. Maltarollo Mariana O. de Godoy Glaucius Oliva Rafael V. C. Guido Mauro M. Teixeira Vivian V. Costa Lirlândia P. Sousa Fernão C. Braga Phytotherapy Research Ouratein D, a Biflavanone From Ouratea spectabilis, Alleviates Betacoronavirus Infection by Mitigating Inflammation, Lung Damage and Viral Replication Adelson Héric A. Monteiro Kátia M. Freitas Ana Clara M. Montuori‐Andrade Erick Bryan Sousa de Lima Antônio Felipe S. Carvalho Camila Cardoso Edvaldo S. Lara Leonardo Camilo Oliveira Isabella Zaidan Felipe Rocha Silva da Santos Filipe Resende Luiz Pedro Souza‐Costa Celso M. Queiroz‐Junior Ian de Meira Chaves Natália R. C. Nóbrega Maria Beatriz O. Rabelo Marina P. Rocha Priscilla R. V. Campana Rodrigo M. Pádua Rafaela S. Ferreira Luiza V. Barreto Thales Kronenberger Vinícius G. Maltarollo Mariana O. de Godoy Glaucius Oliva Rafael V. C. Guido Mauro M. Teixeira Vivian V. Costa Lirlândia P. Sousa Fernão C. Braga Phytotherapy Research ABSTRACTSevere 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 (Mpro). 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 Mpro, and both significantly inhibited Mpro 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 Mpro inhibition, suggesting alternative mechanisms for its antiviral activity. 10.1002/ptr.8462 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Ouratein D, a Biflavanone From Ouratea spectabilis, Alleviates Betacoronavirus Infection by Mitigating Inflammation, Lung Damage and Viral Replication |
| topic | Phytotherapy Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/ptr.8462 |