COVID-19 Supplements: Numerous Studies Show That The Phytochemical Quercetin Not Only Inhibits SARS-CoV-2 But Helps In Other Aspects Of COVID-19

COVID-19 Supplements: Since Thailand Medical News first covered a collection of studies in August 2020 showing that Quercetin could be used as adjuvant to treat COVID-19, its effectiveness has since been proven in many subsequent studies and even randomized clinical trials. https://www.thailandmedical.news/news/breaking-supplements-for-covid-19-quercetin-emerging-as-an-adjuvant-for-covid-19-treatments

Numerous studies have been conducted showing its efficacy not only as an antiviral agent but also as a therapeutic supplement that has  anti-inflammatory and immunomodulatory properties along with tissue and organ protective and repair properties.
 
One study conducted by scientists from Tianjin Medical University that has been published in the peer reviewed Computational and Structural Biotechnology Journal indicates that Quercetin is one of the many phytochemicals in TCM (Traditional Chinese Medicine) herbs that may inhibit SARS-CoV-2 Virus. https://www.sciencedirect.com/science/article/pii/S2001037020304773
 
Using computational methods, the study team identified three phytochemicals in traditional Chinese medicine that could be used against SARS-CoV-2: Quercetin, Puerarin and Kaempferol​. 
 
Significantly of the three compounds, Quercetin showed the highest binding affinity to both the ACE2 receptor and the receptor-binding domain of the SARS-CoV-2 spike protein, and could thus provide a dual synergistic effect.  
 
It has been known that the SARS-CoV-2 coronavirus infects human hosts by binding with the human angiotensin-converting enzyme 2 (ACE2) receptor on their cells, notably the epithelium lining the respiratory tract. The receptor-binding domain (RBD) of the coronavirus spike protein binds to ACE2 followed by membrane fusion to the host cell, thus allowing the virus to infiltrate the cell and commence replication.
 
TCM or Traditional Chinese Medicine, widely used for many diseases, showed therapeutic effects during the 2003 SARS-CoV epidemic.
 
The RBD or receptor-binding domain of the SARS-CoV-2 has significant structural homology with SARS-CoV. Although the use of Chinese herbs with modern medicine has shown benefits in COVID-19 patients, several components are present in the herbs and have complex interactions, making it challenging to uncover the molecular mechanisms responsible for its therapeutic effects.
 
Many computational studies have helped predict active compounds in the medicinal herbs with the potential to accelerate traditional medicine-based drug discovery.
 
The Chinese study team used computational analysis to discover potential molecule candidates against SARS-CoV-2 infection. Utilizing the Traditional Chinese Medicine Pharmacology database, they screened for molecules that could target ACE2.
 
The study team identified the compound puerarin that could target ACE2. Then, they screened for Chinese herbs that have this compound in the database and found five. Furthermore, sinc e it is thought that compounds in the same herbal medicine have synergistic properties, they expanded their search to include all the compounds in the five herbs to arrive at 41 compounds.
 
Upon analyzing which compounds were present in the maximum number of herbs however, they found puerarin was present in all the five herbs, and quercetin and kaempferol were present in three herbs.
 
The team then predicted potential drug targets of the selected compounds using the database, leading to 240 possible targets. Upon further analysis, they selected puerarin, quercetin, and kaempferol for further study.
 
The researchers next performed molecular docking analysis to determine potential binding sites and binding affinity to ACE2. All the three compounds could bind on the same region of ACE2, which is located some distance from the binding position of SARS-CoV-2. It is likely the compounds are causing changes in conformations rather than competing with the spike protein to bind to ACE2.
 
Importantly, it was found that Quercetin had the highest binding affinity, forming both strong and weak hydrogen bonds.
 
The study team also experimentally determined the binding of the three compounds to ACE2 using surface plasmon resonance. Similar to the theoretical analysis, they found quercetin had higher binding affinity to ACE2 than puerarin. They also observed that puerarin affected the binding of spike protein to ACE2, and quercetin almost completely disrupted the spike protein binding to ACE2.


Quercetin could bind to RBD domain of S-protein with a high binding affinity. (A) Hydrophilic-hydrophobic interaction between (i) quercetin and SARS-CoV-2 Spike in candidate protein binding pocket, and (ii) quercetin and relative amino acids. (B) The KD of the SARS-CoV-2 Spike RBD protein with a series of concentrations of quercetin was calculated by SPR.

Importantly molecular docking analysis showed that quercetin has high binding affinity to the spike protein.
 
Utilizing pathway enrichment analysis for the COVID-19-related genes, the study team found quercetin affected the immune-modulation and viral infection activities.
 
It should be noted that Quercetin has been found in all the 26 Chinese herbal medicines advised by traditional Chinese medicine practitioners to combat COVID-19.
 
The phytochemical Quercetin showed a higher binding affinity to both ACE2 and the RBD of the spike protein. The dual binding effect of quercetin could therefore be synergistic and provide a strong antiviral effect against SARS-CoV-2.
 
Also since analysis suggested that quercetin could affect immunomodulation, and because studies have shown patients with severe COVID-19 disease tend to experience cytokine storms, quercetin as one of the any COVID-19 Supplements could help alleviate symptoms in such cases.
 
Two separate randomized clinical trials led by Italian researchers but supported by multinational teams of scientists found that Quercetin not only prevented disease severity and mortality in infected COVID-19 patients, but also resolved clinical symptoms faster and lead to faster viral clearance times.
https://www.dovepress.com/potential-clinical-benefits-of-quercetin-in-the-early-stage-of-covid-1-peer-reviewed-fulltext-article-IJGM
 
https://www.dovepress.com/possible-therapeutic-effects-of-adjuvant-quercetin-supplementation-aga-peer-reviewed-fulltext-article-IJGM
 
Another study conducted by researchers from Iran showed the mechanics by which quercetin could function as an anti-inflammatory compound and prevent cytokine storms in those infected by the SARS-CoV-2. https://journal-inflammation.biomedcentral.com/articles/10.1186/s12950-021-00268-6
 
Studies have also emerged that quercetin can help in the treatment of acute kidney injury as a result of COVID-19, hence showing its potent role for Long COVID as well. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245209
 
Studies are also currently underway with regards to using quercetin as a prophylaxis against SARS-CoV-2 infections.
 
Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; red onions and kale are common foods containing appreciable amounts of quercetin.
 
Quercetin supplements are relative safe to take. In preliminary human studies, oral intake of quercetin in doses up to one gram per day over three months did not cause adverse effects. https://pubmed.ncbi.nlm.nih.gov/17698276/
 
However readers have to be careful when buying quercetin supplements as many supplement brands take advantage of lax regulatory controls over supplements and also weak labeling laws. Thailand Medical News strongly recommends only buying the following brands of quercetin supplements: Thorne Research, Nature’s Way, Natural Factors, Solaray, Doctor’s Best, Natrol and Piping Rock. It is better to buy quercetin along with bromelain for enhanced bioactivity.
 
There are certain American brands including some that we use to recommend in the past but we have since found those brands to be selling inferior products and in some cases we even misrepresenting the contents found in the labeled bottles!
 
For more on COVID-19 Supplements, keep on logging to Thailand Medical News.