Dr. Weeks’ Comment: How curious that the spike protein is what allows the virus to enter the cell and people are told that the jabs turn their cells into “spike protein factories” …. How can THAT be beneficial? But this common weed – the dandelion can interfere with the spike protein threatening you. Get your dandelion in a synergistic blend of detoxifying seeds and greens here. Read on!
Common dandelion (Taraxacum officinale) efficiently blocks the interaction between ACE2 cell surface receptor and SARS-CoV-2 spike protein D614, mutants D614G, N501Y, K417N and E484K in vitro
Hoai Thi Thu Tran1 , Nguyen Phan Khoi Le1 , Michael Gigl2 , Corinna Dawid2 , and Evelyn Lamy1* 1
Molecular Preventive Medicine, University Medical Center and Faculty of Medicine – University of Freiburg, Engesserstraße 4, 79108 Freiburg, Germany 2 Institute of Food Chemistry and Molecular Sensory Science, Technical University of Munich, Lise-Meitner-Str. 34, 85354 Freising, Germany *Correspondence: Address for correspondence: Prof. Dr. Evelyn Lamy Molecular Preventive Medicine, University Medical Center and Faculty of Medicine – University of Freiburg, Engesserstraße 4, 79108 Freiburg, Germany Phone: +49 761 / 270-82150 email: evelyn.lamy@uniklinik-freiburg.de Conflicts of Interest: The authors declare no conflict of interest.
Abstract
On 11th March 2020, coronavirus disease 2019 (COVID‐19), caused by the SARS-CoV-2 virus, was declared as a global pandemic by the World Health Organization (WHO). To date, there are rapidly spreading new “variants of concern“ of SARS-CoV-2, the United Kingdom (B.1.1.7), the South African (B.1.351) or Brasilian (P.1) variant. All of them contain multiple mutations in the ACE2 receptor recognition site of the spike protein, compared to the original Wuhan sequence, which is of great concern, because of their potential for immune escape. Here we report on the efficacy of common dandelion (Taraxacum officinale) to block proteinprotein interaction of spike S1 to the human ACE2 cell surface receptor. This could be shown for the original spike D614, but also for its mutant forms (D614G, N501Y, and mix of K417N, E484K, N501Y) in human HEK293-hACE2 kidney and A549-hACE2-TMPRSS2 lung cells. High molecular weight compounds in the water-based extract account for this effect. Infection of the lung cells using SARS-CoV-2 spike pseudotyped lentivirus particles was efficiently prevented by the extract and so was virus-triggered pro-inflammatory interleukin 6 secretion.
Modern herbal monographs consider the usage of this medicinal plant as safe. Thus, the in vitro results reported here should encourage further research on the clinical relevance and applicability of the extract as prevention strategy for SARS-CoV-2 infection.
Significance statement: SARS-CoV-2 is steadily mutating during continuous transmission among humans. This might eventually lead the virus into evading existing therapeutic and prophylactic approaches aimed at the viral spike. We found effective inhibition of protein-protein interaction between the human virus cell entry receptor ACE2 and SARS-CoV-2 spike, including five relevant mutations, by water-based common dandelion (Taraxacum officinale) extracts.
This was shown in vitro using human kidney (HEK293) and lung (A549) cells, overexpressing the ACE2 and ACE2/TMPRSS2 protein, respectively. Infection of the lung cells using SARS-CoV-2 pseudotyped lentivirus was efficiently prevented by the extract. The results deserve more inmade available under aCC-BY-NC-ND 4.0 International license. (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is bioRxiv preprint doi: https://doi.org/10.1101/2021.03.19.435959; this version posted March 19, 2021. The copyright holder for this preprint depth analysis of dandelions´ effectiveness in SARS-CoV-2 prevention and now require confirmatory clinical evidence.
Introduction: In late 2019, the disease known as Corona Virus Disease 2019 or COVID-19 was first reported (1, 2). It is induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Dry cough, fever, fatigue, headache, myalgias, and diarrhea are common symptoms of the disease. In severe cases people may become critically ill with acute respiratory distress syndrome (3). The SARS-CoV-2 virus surface is covered by a large number of glycosylated S proteins, which consist of two subunits, S1 and S2. The S1 subunit recognizes and attaches to the membrane-anchored carboxypeptidase angiotensin-converting enzyme 2 (ACE2) receptor on the host cell surface through its receptor binding domain (RBD). The S2 subunit plays a key role in mediating virus–cell fusion and in concert with the host transmembrane protease serine subtype 2 (TMPRSS2), promotes cellular entry (4). This interaction between the virus and host cell at entry site is crucial for disease onset and progression.
To date there are three rapidly spreading new variants of SARS-CoV-2 which were first reported in the United Kingdom (variant B.1.1.7), South Africa (variant B.1.351) and Brasil (variant P.1), all of which share the mutation N501Y in the spike protein (5). SARS-CoV-2 variants with spike protein D614G mutations now predominate globally. B.1.351 contains, besides D614G, other spike mutations, including three mutations (K417N, E484K und N501Y) in the RBD (6). Preliminary data suggest a possible association between the observed increased fatality rate with the mutation D614G and it is hypothesized that a conformational change in the spike protein results in increased infectivity (7).
Free energy perturbation calculations for interactions of the N501Y and K417N mutations with both the ACE2 receptor and an antibody derived from COVID-19 patients raise important questions about the possible human immune response and the success of already available vaccines (8). Further, increased resistance of the variants B.1.351 and B.1.1.7 to antibody neutralization has been reported; for B.1.351 this was largely due to the E484K mutation in the spike protein (9).
Interference with the interaction site between the spike S1 subunit and ACE2 has the potential to be a major target for therapy or prevention (10).
Compounds from natural origin may offer here some protection against viral cell entry while have no or few side effects. Here we report on the inhibitory potential of dandelion on the binding of the spike S1 protein RBD to the hACE2 cell surface receptor and compared the effect of the original D614 spike protein to its D614G, N501Y, and mix (K417N, E484K, N501Y) mutations.
The common dandelion (Taraxacum officinale) belongs to the plant family Asteraceae, subfamily Cichorioideae with many varieties and microspecies. It is a perennial herb, native distributed in the warmer temperate zones of the Northern Hemisphere inhabiting fields, roadsides and ruderal sites.
T. officinale is consumed as vegetable food, but also employed in European phytotherapy to treat disorders from the liver, gallbladder, digestive tract or rheumatic diseases. Modern herbal monographs consider the plant usage as safe and have evaluated the empiric use of T. officinale with a positive outcome. Therapeutic indications for the use of T. officinale are listed in the German Commission E, the European Scientific Cooperative for Phytotherapy (ESCOP) monographs (11, 12) as well as in the British Herbal Medicine Association (13).
The plant contains a wide array of phytochemicals including terpenes (sesquiterpene lactones such as taraxinic acid and triterpenes), phenolic compounds (phenolic acids, flavonoids, and coumarins) and also polysaccharides (14). The predominant phenolic compound was found to be chicoric acid (dicaffeoyltartaric acid). The other were mono- and dicaffeoylquinic acids, tartaric acid derivatives, flavone and flavonol glycosides. The roots, in addition to these compound classes, contain high amounts of inulin (15).
Dosage forms include aqueous decoction and infusion, expressed juice of fresh plant, hydroalcoholic tincture as well as coated tablets from dried extracts applied as monopreparations (16) but also integral components of pharmaceutical remedies. Our research was conducted using water-based extracts from plant leaves. We found that leaf extracts efficiently blocked spike protein or its mutant forms to the ACE2 receptor, used in either pre- or post-incubation, and that high molecular weight compounds account for this effect. A plant from the same tribe (Cichorium intybus) could exert similar effects but with less potency. Infection of A549-hACE2- made available under aCC-BY-NC-ND 4.0 I