In vitro and in vivo effects of Pelargonium sidoides DC. root extract EPs® 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2
The occurrence of immune-evasive SARS-CoV-2 strains emphasizes the importance to search for broad-acting antiviral compounds. Our previous in vitro study showed that Pelargonium sidoides DC. root extract EPs® 7630 has combined antiviral and immunomodulatory properties in SARS-CoV-2-infected human lu...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1214351/full |
| _version_ | 1827892990914330624 |
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| author | Jackson Emanuel Jackson Emanuel Jan Papies Jan Papies Celine Galander Celine Galander Julia M. Adler Nicolas Heinemann Nicolas Heinemann Kathrin Eschke Sophie Merz Hannah Pischon Ruben Rose Andi Krumbholz Andi Krumbholz Žarko Kulić Martin D. Lehner Jakob Trimpert Marcel A. Müller Marcel A. Müller |
| author_facet | Jackson Emanuel Jackson Emanuel Jan Papies Jan Papies Celine Galander Celine Galander Julia M. Adler Nicolas Heinemann Nicolas Heinemann Kathrin Eschke Sophie Merz Hannah Pischon Ruben Rose Andi Krumbholz Andi Krumbholz Žarko Kulić Martin D. Lehner Jakob Trimpert Marcel A. Müller Marcel A. Müller |
| author_sort | Jackson Emanuel |
| collection | DOAJ |
| description | The occurrence of immune-evasive SARS-CoV-2 strains emphasizes the importance to search for broad-acting antiviral compounds. Our previous in vitro study showed that Pelargonium sidoides DC. root extract EPs® 7630 has combined antiviral and immunomodulatory properties in SARS-CoV-2-infected human lung cells. Here we assessed in vivo effects of EPs® 7630 in SARS-CoV-2-infected hamsters, and investigated properties of EPs® 7630 and its functionally relevant constituents in context of phenotypically distinct SARS-CoV-2 variants. We show that EPs® 7630 reduced viral load early in the course of infection and displayed significant immunomodulatory properties positively modulating disease progression in hamsters. In addition, we find that EPs® 7630 differentially inhibits SARS-CoV-2 variants in nasal and bronchial human airway epithelial cells. Antiviral effects were more pronounced against Omicron BA.2 compared to B.1 and Delta, the latter two preferring TMPRSS2-mediated fusion with the plasma membrane for cell entry instead of receptor-mediated low pH-dependent endocytosis. By using SARS-CoV-2 Spike VSV-based pseudo particles (VSVpp), we confirm higher EPs® 7630 activity against Omicron Spike-VSVpp, which seems independent of the serine protease TMPRSS2, suggesting that EPs® 7630 targets endosomal entry. We identify at least two molecular constituents of EPs® 7630, i.e., (−)-epigallocatechin and taxifolin with antiviral effects on SARS-CoV-2 replication and cell entry. In summary, our study shows that EPs® 7630 ameliorates disease outcome in SARS-CoV-2-infected hamsters and has enhanced activity against Omicron, apparently by limiting late endosomal SARS-CoV-2 entry. |
| first_indexed | 2024-03-12T21:47:51Z |
| format | Article |
| id | doaj.art-044307d14f644aaf80e4e9beb57d435d |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-12T21:47:51Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-044307d14f644aaf80e4e9beb57d435d2023-07-26T07:10:39ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-07-011410.3389/fphar.2023.12143511214351In vitro and in vivo effects of Pelargonium sidoides DC. root extract EPs® 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2Jackson Emanuel0Jackson Emanuel1Jan Papies2Jan Papies3Celine Galander4Celine Galander5Julia M. Adler6Nicolas Heinemann7Nicolas Heinemann8Kathrin Eschke9Sophie Merz10Hannah Pischon11Ruben Rose12Andi Krumbholz13Andi Krumbholz14Žarko Kulić15Martin D. Lehner16Jakob Trimpert17Marcel A. Müller18Marcel A. Müller19Institute of Virology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyGerman Center for Infection Research (DZIF), Partner Site Charité, Berlin, GermanyInstitute of Virology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyGerman Center for Infection Research (DZIF), Partner Site Charité, Berlin, GermanyInstitute of Virology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyGerman Center for Infection Research (DZIF), Partner Site Charité, Berlin, GermanyInstitut für Virologie, Freie Universität Berlin, Berlin, GermanyInstitute of Virology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyGerman Center for Infection Research (DZIF), Partner Site Charité, Berlin, GermanyInstitut für Virologie, Freie Universität Berlin, Berlin, GermanyIDEXX Laboratories, Kornwestheim, GermanyIDEXX Laboratories, Kornwestheim, GermanyInstitute for Infection Medicine, Kiel University and University Hospital Schleswig-Holstein, Kiel, GermanyInstitute for Infection Medicine, Kiel University and University Hospital Schleswig-Holstein, Kiel, GermanyLabor Dr. Krause und Kollegen MVZ GmbH, Kiel, GermanyPreclinical R&D, Dr. Willmar Schwabe GmbH and Co. KG, Karlsruhe, GermanyPreclinical R&D, Dr. Willmar Schwabe GmbH and Co. KG, Karlsruhe, GermanyInstitut für Virologie, Freie Universität Berlin, Berlin, GermanyInstitute of Virology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, GermanyGerman Center for Infection Research (DZIF), Partner Site Charité, Berlin, GermanyThe occurrence of immune-evasive SARS-CoV-2 strains emphasizes the importance to search for broad-acting antiviral compounds. Our previous in vitro study showed that Pelargonium sidoides DC. root extract EPs® 7630 has combined antiviral and immunomodulatory properties in SARS-CoV-2-infected human lung cells. Here we assessed in vivo effects of EPs® 7630 in SARS-CoV-2-infected hamsters, and investigated properties of EPs® 7630 and its functionally relevant constituents in context of phenotypically distinct SARS-CoV-2 variants. We show that EPs® 7630 reduced viral load early in the course of infection and displayed significant immunomodulatory properties positively modulating disease progression in hamsters. In addition, we find that EPs® 7630 differentially inhibits SARS-CoV-2 variants in nasal and bronchial human airway epithelial cells. Antiviral effects were more pronounced against Omicron BA.2 compared to B.1 and Delta, the latter two preferring TMPRSS2-mediated fusion with the plasma membrane for cell entry instead of receptor-mediated low pH-dependent endocytosis. By using SARS-CoV-2 Spike VSV-based pseudo particles (VSVpp), we confirm higher EPs® 7630 activity against Omicron Spike-VSVpp, which seems independent of the serine protease TMPRSS2, suggesting that EPs® 7630 targets endosomal entry. We identify at least two molecular constituents of EPs® 7630, i.e., (−)-epigallocatechin and taxifolin with antiviral effects on SARS-CoV-2 replication and cell entry. In summary, our study shows that EPs® 7630 ameliorates disease outcome in SARS-CoV-2-infected hamsters and has enhanced activity against Omicron, apparently by limiting late endosomal SARS-CoV-2 entry.https://www.frontiersin.org/articles/10.3389/fphar.2023.1214351/fullSARS-CoV-2coronavirusPelargonium sidoidesEPs 7630drug repurposingimmune modulation |
| spellingShingle | Jackson Emanuel Jackson Emanuel Jan Papies Jan Papies Celine Galander Celine Galander Julia M. Adler Nicolas Heinemann Nicolas Heinemann Kathrin Eschke Sophie Merz Hannah Pischon Ruben Rose Andi Krumbholz Andi Krumbholz Žarko Kulić Martin D. Lehner Jakob Trimpert Marcel A. Müller Marcel A. Müller In vitro and in vivo effects of Pelargonium sidoides DC. root extract EPs® 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2 Frontiers in Pharmacology SARS-CoV-2 coronavirus Pelargonium sidoides EPs 7630 drug repurposing immune modulation |
| title | In vitro and in vivo effects of Pelargonium sidoides DC. root extract EPs® 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2 |
| title_full | In vitro and in vivo effects of Pelargonium sidoides DC. root extract EPs® 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2 |
| title_fullStr | In vitro and in vivo effects of Pelargonium sidoides DC. root extract EPs® 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2 |
| title_full_unstemmed | In vitro and in vivo effects of Pelargonium sidoides DC. root extract EPs® 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2 |
| title_short | In vitro and in vivo effects of Pelargonium sidoides DC. root extract EPs® 7630 and selected constituents against SARS-CoV-2 B.1, Delta AY.4/AY.117 and Omicron BA.2 |
| title_sort | in vitro and in vivo effects of pelargonium sidoides dc root extract eps r 7630 and selected constituents against sars cov 2 b 1 delta ay 4 ay 117 and omicron ba 2 |
| topic | SARS-CoV-2 coronavirus Pelargonium sidoides EPs 7630 drug repurposing immune modulation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1214351/full |
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