Repurposing <i>Astragalus</i> Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health. In an effort to develop novel anti-coronavirus therapeutics and achieve prophylactics, we used gene set enrichment analysis (GSEA...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/3/641 |
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| author | Chia-Yin Lee Anh Thuc Nguyen Ly Hien Doan Li-Wei Chu Chih-Hung Chang Hui-Kang Liu I-Lin Lee Teng-Hsu Wang Jin-Mei Lai Shih-Ming Tsao Hsiu-Jung Liao Yueh-Hsin Ping Chi-Ying F. Huang |
| author_facet | Chia-Yin Lee Anh Thuc Nguyen Ly Hien Doan Li-Wei Chu Chih-Hung Chang Hui-Kang Liu I-Lin Lee Teng-Hsu Wang Jin-Mei Lai Shih-Ming Tsao Hsiu-Jung Liao Yueh-Hsin Ping Chi-Ying F. Huang |
| author_sort | Chia-Yin Lee |
| collection | DOAJ |
| description | The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health. In an effort to develop novel anti-coronavirus therapeutics and achieve prophylactics, we used gene set enrichment analysis (GSEA) for drug screening and identified that <i>Astragalus</i> polysaccharide (PG2), a mixture of polysaccharides purified from <i>Astragalus membranaceus</i>, could effectively reverse COVID-19 signature genes. Further biological assays revealed that PG2 could prevent the fusion of BHK21-expressing wild-type (WT) viral spike (S) protein and Calu-3-expressing ACE2. Additionally, it specifically prevents the binding of recombinant viral S of WT, alpha, and beta strains to ACE2 receptor in our non-cell-based system. In addition, PG2 enhances <i>let-7a</i>, <i>miR-146a</i>, and <i>miR-148b</i> expression levels in the lung epithelial cells. These findings speculate that PG2 has the potential to reduce viral replication in lung and cytokine storm via these PG2-induced miRNAs. Furthermore, macrophage activation is one of the primary issues leading to the complicated condition of COVID-19 patients, and our results revealed that PG2 could regulate the activation of macrophages by promoting the polarization of THP-1-derived macrophages into an anti-inflammatory phenotype. In this study, PG2 stimulated M2 macrophage activation and increased the expression levels of anti-inflammatory cytokines IL-10 and IL-1RN. Additionally, PG2 was recently used to treat patients with severe COVID-19 symptoms by reducing the neutrophil-to-lymphocyte ratio (NLR). Therefore, our data suggest that PG2, a repurposed drug, possesses the potential to prevent WT SARS-CoV-2 S-mediated syncytia formation with the host cells; it also inhibits the binding of S proteins of WT, alpha, and beta strains to the recombinant ACE2 and halts severe COVID-19 development by regulating the polarization of macrophages to M2 cells. |
| first_indexed | 2024-03-11T05:47:02Z |
| format | Article |
| id | doaj.art-554edb2516954da082a36a4b27c73a7a |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T05:47:02Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-554edb2516954da082a36a4b27c73a7a2023-11-17T14:22:17ZengMDPI AGViruses1999-49152023-02-0115364110.3390/v15030641Repurposing <i>Astragalus</i> Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory EffectsChia-Yin Lee0Anh Thuc Nguyen1Ly Hien Doan2Li-Wei Chu3Chih-Hung Chang4Hui-Kang Liu5I-Lin Lee6Teng-Hsu Wang7Jin-Mei Lai8Shih-Ming Tsao9Hsiu-Jung Liao10Yueh-Hsin Ping11Chi-Ying F. Huang12Taiwan National Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei 112304, TaiwanTaiwan National Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei 112304, TaiwanInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112304, TaiwanDepartment and Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, TaiwanDepartment of Orthopedic Surgery, Far Eastern Memorial Hospital, New Taipei City 220216, TaiwanDivision of Basic Chinese Medicine, National Research Institute of Chinese Medicine (NRICM), Ministry of Health and Welfare, Taipei 112304, TaiwanPhytoHeath Corporation, Taipei 105403, TaiwanPhytoHeath Corporation, Taipei 105403, TaiwanDepartment of Life Science, College of Science and Engineering, Fu Jen Catholic University, New Taipei City 242062, TaiwanDivision of Pulmonary Medicine, School of Medicine, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 402306, TaiwanDepartment of Medical Research, Far Eastern Memorial Hospital, New Taipei City 220216, TaiwanDepartment and Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, TaiwanInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112304, TaiwanThe outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health. In an effort to develop novel anti-coronavirus therapeutics and achieve prophylactics, we used gene set enrichment analysis (GSEA) for drug screening and identified that <i>Astragalus</i> polysaccharide (PG2), a mixture of polysaccharides purified from <i>Astragalus membranaceus</i>, could effectively reverse COVID-19 signature genes. Further biological assays revealed that PG2 could prevent the fusion of BHK21-expressing wild-type (WT) viral spike (S) protein and Calu-3-expressing ACE2. Additionally, it specifically prevents the binding of recombinant viral S of WT, alpha, and beta strains to ACE2 receptor in our non-cell-based system. In addition, PG2 enhances <i>let-7a</i>, <i>miR-146a</i>, and <i>miR-148b</i> expression levels in the lung epithelial cells. These findings speculate that PG2 has the potential to reduce viral replication in lung and cytokine storm via these PG2-induced miRNAs. Furthermore, macrophage activation is one of the primary issues leading to the complicated condition of COVID-19 patients, and our results revealed that PG2 could regulate the activation of macrophages by promoting the polarization of THP-1-derived macrophages into an anti-inflammatory phenotype. In this study, PG2 stimulated M2 macrophage activation and increased the expression levels of anti-inflammatory cytokines IL-10 and IL-1RN. Additionally, PG2 was recently used to treat patients with severe COVID-19 symptoms by reducing the neutrophil-to-lymphocyte ratio (NLR). Therefore, our data suggest that PG2, a repurposed drug, possesses the potential to prevent WT SARS-CoV-2 S-mediated syncytia formation with the host cells; it also inhibits the binding of S proteins of WT, alpha, and beta strains to the recombinant ACE2 and halts severe COVID-19 development by regulating the polarization of macrophages to M2 cells.https://www.mdpi.com/1999-4915/15/3/641COVID-19microRNAsmacrophagescytokine stormviral entry |
| spellingShingle | Chia-Yin Lee Anh Thuc Nguyen Ly Hien Doan Li-Wei Chu Chih-Hung Chang Hui-Kang Liu I-Lin Lee Teng-Hsu Wang Jin-Mei Lai Shih-Ming Tsao Hsiu-Jung Liao Yueh-Hsin Ping Chi-Ying F. Huang Repurposing <i>Astragalus</i> Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects Viruses COVID-19 microRNAs macrophages cytokine storm viral entry |
| title | Repurposing <i>Astragalus</i> Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects |
| title_full | Repurposing <i>Astragalus</i> Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects |
| title_fullStr | Repurposing <i>Astragalus</i> Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects |
| title_full_unstemmed | Repurposing <i>Astragalus</i> Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects |
| title_short | Repurposing <i>Astragalus</i> Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects |
| title_sort | repurposing i astragalus i polysaccharide pg2 for inhibiting ace2 and sars cov 2 spike syncytial formation and anti inflammatory effects |
| topic | COVID-19 microRNAs macrophages cytokine storm viral entry |
| url | https://www.mdpi.com/1999-4915/15/3/641 |
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