Secondary metabolites of Alternaria alternate appraisal of their SARS-CoV-2 inhibitory and anti-inflammatory potentials.
This study identifies the secondary metabolites from Alternaria alternate and evaluates their ACE-2: Spike RBD (SARS-CoV-2) inhibitory activity confirmed via immunoblotting in human lung microvascular endothelial cells. In addition, their in vitro anti-inflammatory potential was assessed using a cel...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0313616 |
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| author | Fatma A Moharram Reham R Ibrahim Shahenda Mahgoub Mohamed S Abdel-Aziz Ahmed M Said Hui-Chi Huang Lo-Yun Chen Kuei-Hung Lai Nashwa Hashad Mohamed S Mady |
| author_facet | Fatma A Moharram Reham R Ibrahim Shahenda Mahgoub Mohamed S Abdel-Aziz Ahmed M Said Hui-Chi Huang Lo-Yun Chen Kuei-Hung Lai Nashwa Hashad Mohamed S Mady |
| author_sort | Fatma A Moharram |
| collection | DOAJ |
| description | This study identifies the secondary metabolites from Alternaria alternate and evaluates their ACE-2: Spike RBD (SARS-CoV-2) inhibitory activity confirmed via immunoblotting in human lung microvascular endothelial cells. In addition, their in vitro anti-inflammatory potential was assessed using a cell-based assay in LPS-treated RAW 264.7 macrophage cells. Two novel compounds, altenuline (1), phthalic acid bis (7'/7'' pentyloxy) isohexyl ester (2), along with 1-deoxyrubralactone (3) alternariol-5-O-methyl ether (4) and alternariol (5) were identified. Molecular docking and in vitro studies showed that compounds 2 and 4 were promising to counteract SARS-CoV-2 attachment to human ACE-2. Thus, they are considered promising natural anti-viral agents. SwissADME in silico analysis was conducted to predict the drug-like potential. Immunoblotting analysis confirmed that the tested compounds (1-4) demonstrated downregulation of ACE-2 expression in the endothelial cells from the lungs with variable degrees. Furthermore, the tested compounds (1-4) showed promising anti-inflammatory activities through TNF-α: TNFR2 inhibitory activity and their inhibitory effect on the proinflammatory cytokines (TNF-α and IL-6) in LPS-stimulated monocytes. In conclusion, our study, for the first time, provides beneficial experimental confirmation for the efficiency of the A. alternate secondary metabolites for the treatment of COVID-19 as they hinder SARS-CoV-2 infection and lower inflammatory responses initiated by SARS-CoV-2. A. alternate and its metabolites are considered in developing preventative and therapeutic tactics for COVID-19. |
| format | Article |
| id | doaj-art-758bb114c85941a789f86bbe89b4b3fa |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-758bb114c85941a789f86bbe89b4b3fa2025-08-20T01:48:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031361610.1371/journal.pone.0313616Secondary metabolites of Alternaria alternate appraisal of their SARS-CoV-2 inhibitory and anti-inflammatory potentials.Fatma A MoharramReham R IbrahimShahenda MahgoubMohamed S Abdel-AzizAhmed M SaidHui-Chi HuangLo-Yun ChenKuei-Hung LaiNashwa HashadMohamed S MadyThis study identifies the secondary metabolites from Alternaria alternate and evaluates their ACE-2: Spike RBD (SARS-CoV-2) inhibitory activity confirmed via immunoblotting in human lung microvascular endothelial cells. In addition, their in vitro anti-inflammatory potential was assessed using a cell-based assay in LPS-treated RAW 264.7 macrophage cells. Two novel compounds, altenuline (1), phthalic acid bis (7'/7'' pentyloxy) isohexyl ester (2), along with 1-deoxyrubralactone (3) alternariol-5-O-methyl ether (4) and alternariol (5) were identified. Molecular docking and in vitro studies showed that compounds 2 and 4 were promising to counteract SARS-CoV-2 attachment to human ACE-2. Thus, they are considered promising natural anti-viral agents. SwissADME in silico analysis was conducted to predict the drug-like potential. Immunoblotting analysis confirmed that the tested compounds (1-4) demonstrated downregulation of ACE-2 expression in the endothelial cells from the lungs with variable degrees. Furthermore, the tested compounds (1-4) showed promising anti-inflammatory activities through TNF-α: TNFR2 inhibitory activity and their inhibitory effect on the proinflammatory cytokines (TNF-α and IL-6) in LPS-stimulated monocytes. In conclusion, our study, for the first time, provides beneficial experimental confirmation for the efficiency of the A. alternate secondary metabolites for the treatment of COVID-19 as they hinder SARS-CoV-2 infection and lower inflammatory responses initiated by SARS-CoV-2. A. alternate and its metabolites are considered in developing preventative and therapeutic tactics for COVID-19.https://doi.org/10.1371/journal.pone.0313616 |
| spellingShingle | Fatma A Moharram Reham R Ibrahim Shahenda Mahgoub Mohamed S Abdel-Aziz Ahmed M Said Hui-Chi Huang Lo-Yun Chen Kuei-Hung Lai Nashwa Hashad Mohamed S Mady Secondary metabolites of Alternaria alternate appraisal of their SARS-CoV-2 inhibitory and anti-inflammatory potentials. PLoS ONE |
| title | Secondary metabolites of Alternaria alternate appraisal of their SARS-CoV-2 inhibitory and anti-inflammatory potentials. |
| title_full | Secondary metabolites of Alternaria alternate appraisal of their SARS-CoV-2 inhibitory and anti-inflammatory potentials. |
| title_fullStr | Secondary metabolites of Alternaria alternate appraisal of their SARS-CoV-2 inhibitory and anti-inflammatory potentials. |
| title_full_unstemmed | Secondary metabolites of Alternaria alternate appraisal of their SARS-CoV-2 inhibitory and anti-inflammatory potentials. |
| title_short | Secondary metabolites of Alternaria alternate appraisal of their SARS-CoV-2 inhibitory and anti-inflammatory potentials. |
| title_sort | secondary metabolites of alternaria alternate appraisal of their sars cov 2 inhibitory and anti inflammatory potentials |
| url | https://doi.org/10.1371/journal.pone.0313616 |
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