{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:41:54Z","timestamp":1791510114515,"version":"4.3.4"},"reference-count":111,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Treatment options for COVID-19 are currently limited. Drugs reducing both viral loads and SARS-CoV-2-induced inflammatory responses would be ideal candidates for COVID-19 therapeutics. Previous\n                    <jats:italic>in vitro<\/jats:italic>\n                    and clinical studies suggest that the proprietary\n                    <jats:italic>Pelargonium sidoides DC.<\/jats:italic>\n                    root extract EPs 7630 has antiviral and immunomodulatory properties, limiting symptom severity and disease duration of infections with several upper respiratory viruses. Here we assessed if EPs 7630 affects SARS-CoV-2 propagation and the innate immune response in the human lung cell line Calu-3. In direct comparison to other highly pathogenic CoV (SARS-CoV, MERS-CoV), SARS-CoV-2 growth was most efficiently inhibited at a non-toxic concentration with an IC50 of 1.61\u00a0\u03bcg\/ml. Particularly, the cellular entry step of SARS-CoV-2 was significantly reduced by EPs 7630 pretreatment (10\u2013100\u00a0\u03bcg\/ml) as shown by spike protein-carrying pseudovirus particles and infectious SARS-CoV-2. Using sequential ultrafiltration, EPs 7630 was separated into fractions containing either prodelphinidins of different oligomerization degrees or small molecule constituents like benzopyranones and purine derivatives. Prodelphinidins with a low oligomerization degree and small molecule constituents were most efficient in inhibiting SARS-CoV-2 entry already at 10\u00a0\u03bcg\/ml and had comparable effects on immune gene regulation as EPs 7630. Downregulation of multiple pro-inflammatory genes (\n                    <jats:italic>CCL5<\/jats:italic>\n                    ,\n                    <jats:italic>IL6<\/jats:italic>\n                    ,\n                    <jats:italic>IL1B<\/jats:italic>\n                    ) was accompanied by upregulation of anti-inflammatory\n                    <jats:italic>TNFAIP3<\/jats:italic>\n                    at 48\u00a0h post-infection. At high concentrations (100\u00a0\u03bcg\/ml) moderately oligomerized prodelphinidins reduced SARS-CoV-2 propagation most efficiently and exhibited pronounced immune gene modulation. Assessment of cytokine secretion in EPs 7630-treated and SARS-CoV-2-coinfected Calu-3 cells showed that pro-inflammatory cytokines IL-1\u03b2 and IL-6 were elevated whereas multiple other COVID-19-associated cytokines (IL-8, IL-13, TNF-\u03b1), chemokines (CXCL9, CXCL10), and growth factors (PDGF, VEGF-A, CD40L) were significantly reduced by EPs 7630. SARS-CoV-2 entry inhibition and the differential immunomodulatory functions of EPs 7630 against SARS-CoV-2 encourage further\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2021.757666","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T02:07:17Z","timestamp":1635127637000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Antiviral and Immunomodulatory Effects of Pelargonium sidoides DC. Root Extract EPs\u00ae 7630 in SARS-CoV-2-Infected Human Lung Cells"],"prefix":"10.3389","volume":"12","author":[{"given":"Jan","family":"Papies","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackson","family":"Emanuel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Heinemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017darko","family":"Kuli\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Schroeder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Tenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin D.","family":"Lehner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Seifert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel A.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1866","DOI":"10.1056\/NEJMc2100362","article-title":"New SARS-CoV-2 Variants - Clinical, Public Health, and Vaccine Implications","volume":"384","author":"Abdool Karim","year":"2021","journal-title":"N. 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