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The recommended dosage is 4–10 g (about 20-30 mg per ml hot water) up to 3 times per day (Commission E and ESCOP). Based on the information provided by the European Medicines Agency (EMA) contraindications for the use of T. officinale are hypersensitivity to the Asteraceae plant family or their active compounds, liver and biliary diseases, including bile duct obstruction, gallstones and cholangitis, or active peptic ulcer (16). The plant is a significant source of potassium (26, 27) and thus a warning is given because of the possible risk for hyperkalaemia.
While in silico docking experiments suggested different common natural compounds as ACE2 inhibitors, spike binding inhibition to ACE2 has not been shown for most of them so far, which might be explained by a lack of complete coverage of ACE2 binding residues by the compounds (20). However, for glycyrrhizin, nobiletin, and neohesperidin, ACE2 binding falls partially within the RBD contact region and thus, these have been proposed to additionally block spike binding to ACE2 (20). The same accounts for synthetic ACE2 inhibitors, such as N-(2-aminoethyl)-1 aziridine-ethanamine (NAAE) (21). In contrast, the lipoglycopeptide antibiotic dalbavancin has now been identified as both, ACE2 binder and SARS-CoV-2 spike-ACE2 inhibitor (22); SARS-CoV-2 infection was effectively inhibited in both mouse and rhesus macaque models by this compound. Also, for a hydroalcoholic pomegranate peel extract, blocking of spike-ACE2 interaction was shown at 74%, for its main constituents punicalagin at 64%, and ellagic acid at 36%. Using SARS-CoV-2 spike pseudotyped lentivirus infection of human kidney-2 (HK-2) cells, virus entry was then efficiently blocked by the peel extract (23). In the present study, we could show potent ACE2-spike S1 RBD protein inhibition by T. officinale extracts using a cell-free assay and confirmed this finding by demonstrating efficient ACE2 cell surface binding inhibition in two human cell lines.
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