Dandelion extract inhibits SARS-CoV-2 in vitro

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen, has caused over 123.7 million cases and over 2.7 million deaths worldwide. In the absence of effective antivirals, its treatment and prevention have been limited to general therapeutic modalities and non-pharmaceutical interventions, despite intensive research aimed at developing better drugs.

An exciting new study that appeared recently on the bioRxiv* server describes a specific inhibitor of the virus found in an extract of the common dandelion that could provide a new and fruitful avenue of drug research.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Recently emerged variants of concern

The SARS-CoV-2 virus has undergone a large number of mutations over the pandemic period. Recently, three rapidly spreading and, in some cases, more virulent, strains of the virus have emerged.

These are known as the United Kingdom (variant B.1.1.7), South African (variant B.1.351) and Brazil (variant P.1). All share the defining spike protein mutation N501Y. All three have descended from an earlier strain carrying the D614G spike mutation that has rapidly become dominant.

The South African variant carries two other important spike mutations, K417N and E484K. Early results indicated the D614G mutation might be associated with higher fatality rates, while the conformational change in the spike protein could lead to higher infectivity.

Effects of VOC mutations

The N501Y and K417N mutations seem to have favorable energetics during their interactions with the host cell receptor for the virus, the angiotensin-converting enzyme 2 (ACE2), suggesting a possibility of higher infectivity.

The same trend is seen during interactions between the spike protein and a natural neutralizing antibody isolated from COVID-19 patients. This raises important concerns about whether the immune response remains protective against these newer variants.

These variants also show resistance to neutralization by existing antibodies, mostly because of the E484K mutation.

Study aims

In view of this, therapeutics that target the spike-ACE2 interactions may be a successful line of study. The current study focuses on inhibition of the binding of the spike-ACE2 proteins via the spike receptor-binding domain (RBD) in the context of the D614 spike, the D614G mutation, the N501Y mutation, and the triple mutation K417N, E484K, and N501Y.

The common dandelion (Taraxacum officinale) is a perennial, native to warm temperate zones in the Northern hemisphere, and widely distributed across road margins, fields, gardens and any other open spaces where it is permitted to grow.

It is an edible plant and has a reputation in Europe as a medicinal plant, touted to be useful in the treatment of illnesses affecting the liver and gallbladder, the gut, and the joints. Its safety has been the subject of many new monographs.

This plant contains terpenes, phenolics including coumarins and flavonoids, and polysaccharides. The most abundant phenolic compound was chicoric acid. The roots contain an abundance of the non-soluble polysaccharide inulin.

Inhibition of spike-ACE2 binding

The administration of water-based extracts from plant leaves was found to be associated with efficient and dose-dependent inhibition of spike protein to the ACE2 receptor, when added before or after incubation of the two.

A related plant, Cichorium intybus, also inhibited this interaction but was not so powerful. The concentration at which these were observed to be effective against 50% of spike-ACE2 interactions (50% effective concentration, EC50) was 12 mg/mL and 30 mg/mL, respectively.

The inhibitory effects were traced to high molecular weight bioactive compounds in the extract.

Inhibition of spike-cell surface binding

The researchers also observed that lung cells in culture, expressing the host cell protein ACE2, failed to bind spike when incubated with the extract first. Binding was reduced by 77%, while the high molecular weight fraction alone blocked binding by 63%.

Continued inhibition at 50% was observed at 3 hours, and at 37% for the chicory extract.

Effects of different mutations on cell-spike binding

When the cultured cells were challenged with the spike D614 and its variants, the binding affinity of the spike to the surface ACE2 was increased by about 1.5-fold and 3-4-fold with the D614G and N501Y mutations, respectively.

If the cell was treated beforehand with the T. officinale extract, there was a rapid inhibition of spike-ACE2 binding within 30 seconds. The inhibition rate was about 60% for the D614 variant, but increased to 88% with both the above mutations.

With chicory leaf extract, the binding inhibition was less potent by 30-70% for the different variants. The effect was still weaker at body temperature.

When added post-incubation, the extract was found to rapidly displace the spike from the spike-receptor complex by 50%, on average, while chicory displaced a quarter of bound spike protein. These results were replicated in human cells in culture.

ACE2-TMPRSS2-expressing cells

The study also involved assessing the spike's binding to the ACE2 receptor in human lung cells expressing both ACE2 and the serine protease TMPRSS2, which is essential for spike-mediated virus-membrane fusion. Interestingly, when added to these cells, the chicory extract showed more potent binding inhibition.

Pretreatment with the extract led to 75% inhibition of binding with T. officinale and 56% for the chicory extract. The IC50 was 1.7 mg/mL.

Post-incubation treatment resulted in comparable results for both D614 and D614G, but a somewhat lower inhibition efficiency for N501Y. The triple mutation spike also showed the same inhibition in the presence of the dandelion extract, with about 80% inhibition irrespective of the time of extract treatment.

Effects on cell viability and extract stability

These extracts remained stable in saliva and significantly reduced the expression of the ACE2 protein, just like the spike. The catalytic activity of the ACE2 enzyme was unimpaired in the presence of the extract at 24 hours, and cell viability remained unchanged after 84 hours.

Pseudovirus inhibition

The results also showed that the dandelion extract blocked viral entry into cells, using a pseudotyped lentivirus expressing the SARS-CoV-2 spike, by about 85% at a concentration of 20 mg/ml, and by 70% at half this concentration.

This was accompanied by anti-inflammatory effects, as reflected by lower levels of the potent inflammatory cytokine interleukin (IL)-6 in the ACE2/TMPRSS2-expressing cells.

What are the implications?

Natural compounds could yield effective and safe antiviral therapeutics and have been reported for many decades. Compounds like glycyrrhizin show inhibition of the ACE2 receptor. However, they may also produce incomplete occlusion of the RBD contact motif, thus preventing spike-ACE2 binding.

Synthetic inhibitors of ACE2 binding like N-(2-aminoethyl)-1 aziridine-ethanamine (NAAE) also show the same behavior. The antibiotic dalbavancin both binds ACE2 and inhibits spike-ACE2 binding, and effectively inhibited infection by this virus in mouse and non-human primate models.

Pomegranate peel extract also showed 74% inhibition of this interaction, and blocking of viral entry into human kidney cells in culture.

Dandelion extract moves beyond this, with potent inhibition of spike-ACE2 binding, confirmed by inhibition of ACE2-cell surface binding in two different human cell lines.

The study also shows that the variants D614G and N501Y show increased binding strength to the ACE2 receptor of human cells. This failed to reflect in reduced strength of inhibition by dandelion extract, both pre- and post-incubation, however.

These being more infectious strains, such efficacy shown by the extract shows great promise against infection by variants of concern.

The high margin of safety is an additional recommendation, with a dosage of 4-10 g 1-3 times a day, and no reported case of overdosage so far. Few contraindications exist but include hypersensitivity, diseases of the biliary tract, or active peptic ulcer disease. Dandelion extract is also high in potassium which may potentially cause hyperkalemia.

The downregulation of ACE2 in the cells following treatment with this extract requires further research to explore its potential impact on human physiology. However, this extract could conceivably be used to block virus binding to the oral mucosa, for instance, after exposure to a COVID-19 case.

This exploits the observed rapid blockade of virus-cell binding and the spike's displacement from already formed spike-ACE2 complexes. The cell experiments underline the relevance of this activity.

Factors such as low toxicity in humans and effective binding inhibition of five relevant spike mutations to the human ACE2 receptor, as reported here in vitro, encourage for more in-depth analysis of T. officinales’ effectiveness in SARS-CoV-2 prevention.”

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Journal references:

Article Revisions

  • Feb 23 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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  1. Nicholas Morrish Nicholas Morrish United States says:

    This paper is flawed, as they used HEK-293 cells, rather than the typically used HEK-293T cells(human kidney cells infected with SV40). Previous research had shown that regular HEK-293 cells do not create an appropriate amplification level and also were flawed as the cells were able to fight off infections on their own. If they repeat this with HEK-293T cells, they will not get the same results. This just goes to show that many aren't understanding the COVID-19 is a complication due to SARS-COV-2 reacting with other RNA/DNA virus's that have been dormant in the host, and that those without such infections don't suffer major effects of SARS-COV-2.

    • Jason A. Jason A. Canada says:

      I would be very interested to read the research you’re basing your claim on.

    • Mary Beth E Mary Beth E United States says:

      I too am interested in knowing your source.

      The full text Abstract shows HEK293 A549-hACE2-TMPRSS2 cells from Germany were used in the study [1]. There are many suppliers of human embryonic kidney 293 (HEK-293)-derived cell lines, specifically designed for COVID-19 studies. For example, InvivoGen's ACE2-(TMPRSS2) cells express high levels of the host receptor ACE2 alone, or in combination with the host protease TMPRSS2, at their cell surface. Thus, these cells are permissive to infection by SARS-CoV-2 and Spike-pseudotyped lentiviral particles. Of note, the addition of TMPRSS2 in A549 cells only significantly increases their infectivity [in-house data]. This cell line collection is ideal for screening small molecule inhibitors and neutralizing antibodies that aim to block the virus-host interaction and cellular signaling outcomes [2].

      293T cells are derived from the human embryonic kidney 293 cell line. 293T cells contain the simian virus 40 (SV40) large T-antigen, which facilitates replication of transfected plasmids containing the SV40 origin of replication. 293T/ACE2 cells are transfected to express ACE2, AND HAVE BEEN USED FOR MANY SARS-COV CELL-CELL FUSION AND PSEUDOVIRUS ENTRY INHIBITOR STUDIES [3]. All caps for emphasis. That 293T has been used for many studies does not mean they are the only cells that can or should be used.

      Source 1:  www.biorxiv.org/.../2021.03.19.435959v1.full
      Source 2:  https://www.invivogen.com/covid-19-related-cells
      Source3 :  https://covdb.stanford.edu/cells-list/

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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