Frontiers in Pharmacology | |
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 | |
Pharmacology | |
Sophie Merz1  Hannah Pischon1  Kathrin Eschke2  Jakob Trimpert2  Julia M. Adler2  Ruben Rose3  Andi Krumbholz4  Celine Galander5  Jan Papies5  Nicolas Heinemann5  Marcel A. Müller5  Jackson Emanuel5  Martin D. Lehner6  Žarko Kulić6  | |
[1] IDEXX Laboratories, Kornwestheim, Germany;Institut für Virologie, Freie Universität Berlin, Berlin, Germany;Institute for Infection Medicine, Kiel University and University Hospital Schleswig-Holstein, Kiel, Germany;Institute for Infection Medicine, Kiel University and University Hospital Schleswig-Holstein, Kiel, Germany;Labor Dr. Krause und Kollegen MVZ GmbH, Kiel, Germany;Institute of Virology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany;German Center for Infection Research (DZIF), Partner Site Charité, Berlin, Germany;Preclinical R&D, Dr. Willmar Schwabe GmbH and Co. KG, Karlsruhe, Germany; | |
关键词: SARS-CoV-2; coronavirus; Pelargonium sidoides; EPs 7630; drug repurposing; immune modulation; COVID-19; cytokine storm; | |
DOI : 10.3389/fphar.2023.1214351 | |
received in 2023-04-29, accepted in 2023-07-11, 发布年份 2023 | |
来源: Frontiers | |
【 摘 要 】
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.
【 授权许可】
Unknown
Copyright © 2023 Emanuel, Papies, Galander, Adler, Heinemann, Eschke, Merz, Pischon, Rose, Krumbholz, Kulić, Lehner, Trimpert and Müller.
【 预 览 】
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