While the novel coronavirus keeps marching across the globe, causing new cases and spreading the panic, a team of Canadian researchers is placing their hopes on Quercetin, a natural flavonoid from plants. The research is led by Dr Michael Chrétien, a scientist at the Clinical Research Institute of Montreal along with Majambu Mbikay, Congolese scientist, to conduct clinical trials on the drug in China and find out if it will test against the novel coronavirus. Dr Chrétien defines Quercetin a “broad-spectrum antiviral” that has shown to be effective against SARS, the Ebola virus, and the Zika virus. Moreover, Quercetin has many other useful properties that will bring benefits to those who are not infected. Let’s not drag this out into a lifetime special and figure out if there is any hope for the cure.
What is Covid-19?
In short, COVID-19 is an illness caused by a coronavirus. Human coronaviruses are common and are typically associated with respiratory infections, from the common cold to severe ones. SARS-CoV-2, a positive-sense single-stranded coronavirus caused the outbreak of COVID-19. Transmission happens mostly via airborne droplets from coughs and sneezes within a range of up to two metres. Indirect contact is also possible via contaminated surfaces, but can’t survive on cardboard for more than one day or on copper for more than several hours and may be inactivated by soap or disinfectants. The incubation period for COVID-19, a period from when a person is infected with the virus to when they develop symptoms, lasts 5-6 days but may range from two to 14 days. The latest findings have shown that SARS-CoV-2 might remain detectable up to 37 days. After entering the human body, the virus starts to replicate. The immune system is not prepared to recognise the new types of viruses and effectively resist them.
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Coronavirus biology
In order to understand what can help with coronavirus, it’s worth knowing how it affects our bodies. The success story of each virus looks similar: get into a human cell, reproduce, damage the cell, and keep on infecting adjacent cells.
Entrance
COVID-19 can get into body cells by attaching to ACE-2, a protein on the cell surface that has many beneficial effects in the organs. Coronavirus can bind to ACE-2, sequestering them from the cell surface and making them lose their activity. This loss of function can lead to serious consequences, such as severe pneumonia, heart failure, and circulatory collapse. Studies on mice infected with SARS, which is close to COVID-19, have shown that a high level of ACE-2 may alleviate the severity of pneumonia. This fact may explain different reactions to novel coronavirus: ACE-2 activity is higher in younger animals than older ones. Such conditions as smoking, older age, diabetes, high blood pressure and heart disease are related to low ACE-2 activity. The development of COVID-19 from common viral illness to severe pneumonia may indicate the loss of ACE2 function, which may lead to enhanced neutrophil infiltration in the lungs and leads to exaggerated inflammation and injury.
Replication
As long as coronavirus enters human cells, it begins to replicate by hijacking mTOR, mammalian target of rapamycin, which is present in all cells. The mTOR is a protein kinase that controls protein synthesis and cell growth in response to nutrients, growth factors, energy levels, and stress. The body uses specialised proteins called Sirtuins to regulate organismal lifespan as well as oxidative stress and DNA damages, and mTOR activation. The activation of Sirtuins can suppress mTOR.
Damage
Once they have multiplied, coronaviruses damage human cells by producing an enzyme called 3CL protease, which allows them to spread to adjacent cells. 3CL protease has been called “the Achilles heel” of coronavirus and is the subject of new antiviral drug development. Some dietary flavonoids inhibit 3CL protease, which may limit the severity of the novel infection.
Doing its dirty work, the virus manages to avoid the immune system that helps to kill viruses. It is unclear if stimulation of immunity may increase the protective abilities of the body. However, weak immunity may contribute to complications. As long as pneumonia develops, the immune system response changes and becomes too active, causing more damage. Therefore, therapies for immune-boosting may be contra-indicated during severe COVID-19 infection.
How to prevent spreading the virus?
During the Covid-19 pandemic, hygiene is a must. As long as there is no vaccine and treatment is focused on symptoms alleviation, preventive measures are a good idea to reduce the chances of infection. These measures include:
- frequent handwashing with soap and warm water for at least 20 seconds
- avoiding touching the eyes, nose, or mouth with unwashed hands
- using a tissue when coughing or sneezing,
- avoiding public and crowded places
- restricting travel
- staying at home
No fun, no parties approach may sound boring, but it is a social distancing that helps to reduce contact of infected persons with healthy people and especially vulnerable ones. Social distancing also includes that people stay approx. 2 meters apart.
So far, no antiviral drugs are approved for the prevention or treatment of human coronavirus infections. Earlier scientists have started to research Quercetin and its antiviral properties and potential effects for Covid-19.
What is Quercetin?
It is highly likely that you’ve tried Quercetin without knowing. Quercetin is a pigment found in many fruits, vegetables, and plants. Quercetin belongs to a family of bioflavonoids, responsible for the bright colours and medicinal properties of many plants. Quercetin is one of the more versatile flavonoids found in cannabis plants. You can get Quercetin through a balanced diet or as a food supplement. Foods and drinks that contain Quercetin include berries, apples, citrus fruits, kale, tomatoes, onions, buckwheat, red wine, and black tea. It is also found in herbal remedies, such as ginkgo biloba and St John’s wort. Quercetin can be taken as a supplement in addition to other products. It can act as an antioxidant, neutralising free radicals that cause cellular and DNA damage. Quercetin is known for its antibacterial and anti-inflammation properties, ability to prevent neurological diseases, and lower high blood pressure.
How can Quercetin help with the novel coronavirus?
Besides anti-inflammatory, anti-mutagens and anti-cancer-causing properties, Quercetin is considered to produce an antiviral effect and the ability to control major cell enzyme functions. Quercetin is considered to have the potential to act against the novel coronavirus and here are the mechanisms that prove its potential:
Inhibition of 3C-like protease (3CLpro)
To enter the cell, CoV binds to a host cell surface receptor – Angiotensin-Converting Enzyme 2 (ACE2) in the case of the novel coronavirus. As soon as it enters the host cell, the virus RNA attaches to the host ribosome for translation of coterminal polyproteins. This is accompanied by a breakdown of proteins into smaller polypeptides or amino acids. This process is called proteolysis and is important for packing new viral parts. The coronavirus’ main proteinase (3CLpro) and the papain-like protease (PLpro) are involved in the proteolysis process and therefore, are essential for the virus.
A 2019 study by Korean scientists has shown that Quercetin and other flavonoids might inhibit the proteolytic activity of SARS-CoV 3C-like protease and therefore cause the antiviral effect.
Prevention from ACE 2 binding
Coronavirus uses the ACE 2 receptor to get into body cells, empty its RNA content and hijack it, and produce more viruses. Therefore, preventing SARS-CoV-2 from binding to the ACE 2 receptor means the virus can’t get into body cells. A computer modelling study has shown that Quercetin, similarly to other compounds, may block the novel coronavirus from entering cells.
mTOR Modulation
Quercetin can act as a nutritional stimulator of Sirtuin function and inhibit mTOR activity. It means that it challenges the replication of the virus. As Quercetin is poorly absorbed, it is best to start taking it as a supplement long before exposure, so it has time to accumulate. Additionally, Quercetin has good safety profiles and causes an anti-inflammatory effect.
The virus weakening
Naturally occurring flavonoids such as Quercetin has shown to be effective against herpes simplex virus type 1 (HSV-1), polio-virus type 1, parainfluenza virus type 3 (Pf-3), and respiratory syncytial virus (RSV) when studied in vitro in cell culture monolayers with the use of the viral plaque reduction technique. During the study, Quercetin caused a concentration-dependent reduction in the infectivity of each virus. Moreover, it reduced the intracellular replication of each virus.
Other studies have suggested that Quercetin has antiviral activity against HIV-luc/SARS, with very low cytotoxicity. Quercetin has been shown to inhibit influenza infection with a broad spectrum of strains, including H1N1 and H3N2 with half-maximal inhibitory concentration. Additionally, Quercetin could suppress the entry of the H5N1 virus with the use of the pseudovirus-based drug screening system. A 2016 study indicates that Quercetin causing inhibitory activity in the early stage of influenza infection may be a future therapeutic option to create safe, effective and affordable natural products for the treatment and prophylaxis of Influenza A viruses (IAVs).
Are there any studies on Quercetin in 2020?
After the outbreak of SARS epidemic, Chrétien and Mbikay, researchers from the Clinical Research Institute of Montreal (IRCM), began studying antiviral properties of Quercetin. This is a significant fact as COVID-19 comes from the same family and is structurally similar to the SARS virus. The novel coronavirus is known as SARS-CoV-2. Earlier research, published in 2014 in Antimicrobial Agents and Chemotherapy stated that a glucosylated form of Quercetin might target steps of viral entry and protect mice against the Ebola virus. The team also discovered that pre-treatment with Quercetin, rather than post-treatment, brought the most reliable protection.
In 2020, Michel Chrétien received a 1 million dollar donation to begin a clinical trial on Quercetin as a potential antiviral drug to fight the novel coronavirus. That plan was to send samples of Quercetin to the Chinese Academy of Sciences in Wuhan, but as the virus is controlled in Montreal, it may have to move back. Canadian and Chinese scientists would cooperate on the trials, which would include about 1,000 test patients. In this study, half the patients would receive Quercetin and half a sugar pill to determine if those consuming Quercetin result in contracting COVID-19 less often. The Food and Drug Administration (FDA) has approved Quercetin as safe for human consumption, meaning that animal testing can be skipped. Undoubtedly, quercetin effectiveness against COVID-19 is yet to be proven, and Dr Chrétien would not like to give “false hope.” However, taking into account the positive results of earlier studies, the hopes for Quercetin are still high.
So far, there are more than 80 clinical trials on potential Covid-19 treatments in China, not including studies in other countries. So one of the biggest aims is searching for a treatment for the dangerous coronavirus strain.
What else is good about Quercetin?
Some patients infected with COVID-19 are being treated with antivirals, that may cost up to thousands of US dollars. In contrast, Quercetin is much cheaper. Moreover, it is a natural supplement and can be taken from ordinary products. Quercetin is an oral drug, which is more convenient than other antiviral intravenous medicines. Creating the vaccine or an affordable treatment for the novel coronavirus can take a long time.
Using the medications or supplements currently available on the market can already improve the coronavirus crisis.
What are other health benefits of Quercetin?
Inflammation
Inflammation is a healthy and necessary body reaction that helps it to fight infections. On the other hand, chronic inflammation brings no good. Studies show that flavonoids, including Quercetin, may alleviate some inflammation-related symptoms by inhibiting cytokines production. Quercetin has proven to be useful for people with rheumatoid arthritis as it may help with the symptoms, such as after-activity pain and swollen joints.
Allergy
Quercetin, known for its antioxidant activity and anti-allergic properties, may stimulate the immune system and antiviral activity, reduce cytokines and leukotrienes production, inhibit the release of histamine, and suppress the production of interleukin IL-4 and influence many other physiological processes. These properties contribute to the immunomodulating and anti-inflammatory properties of Quercetin and make it helpful in the treatment of bronchial asthma responses, allergic rhinitis and some anaphylactic reactions.
Blood pressure
High blood pressure can contribute to the risk of heart diseases. Scientific research suggests that Quercetin may reduce blood pressure. Studies on rats have shown that Quercetin may have a relaxing effect on blood vessels and lower systolic and diastolic blood pressure values. Even though the study results look promising, further human studies are needed to prove that the flavonoid may become an alternative for the treatment of high blood pressure.
Brain conditions
Antioxidant properties and neuroprotective effects of Quercetin may help protect against degenerative brain disorders, such as Alzheimer’s disease and improve brain function. In addition to an antioxidant effect, Quercetin may also stimulate cellular protection against oxidative stress. Even though these results are promising, further research in humans is needed.
Ageing
Quercetin may help slow down ageing. Animal studies have shown that Quercetin may help rejuvenate, remove ageing cells and reduce ageing markers. According to the study results, Quercetin and its combination with Resveratrol may increase levels of antioxidants, lower ageing markers in hyperglycemia-mediated oxidative stress in hyperglycemia conditions. These results have shown that flavonoids such as Resveratrol prove to have anti-ageing potential. However, more human research is needed.
Is Quercetin Safe?
Quercetin is relatively safe for most people if taken by mouth short-term. According to studies, Quercetin may be safely used in amounts up to 500 mg twice daily for 12 weeks. However, it is not known if high doses or long-term will not cause any complications. Very high doses of Quercetin may cause kidney damage. Some people have reported headaches, upset stomach and tingling of the arms and legs when taking Quercetin orally.
Quercetin is potentially safe when taken intravenously in appropriate amounts (less than 722 mg). Possible side effects may include sweating, flushing, nausea, vomiting, shortness of breath, or pain at the injection site. High amounts given intravenously may be unsafe. There were reports about kidney damage at higher doses, more than 1 gram per day. Quercetin may worsen kidney problems and is not recommended in such conditions.
There is a lack of valid information if Quercetin is safe to use for pregnant or breastfeeding women. Very high doses might cause kidney damage. Quercetin was also shown to worsen estrogen-induced breast tumours in rats.
Does Quercetin interact with other medications?
Quercetin can also interact with medicines. Taking Quercetin may lessen the effectiveness of some antibiotics. Quercetin may reduce the ability of the liver to break down some drugs. Taking Quercetin might increase the effects and side effects of some medications, such as CYP3A4 or CYP2C19 substrate drugs. Due to its antioxidant effects, Quercetin may interfere with the actions of chemotherapy drugs.
Some fruit extracts, such as papaya and Bromelain, may increase the absorption of Quercetin in the intestine.
It is worth remembering that some supplements may not be tested for safety, and the content of some products may differ from what is written on the label. Keep in mind that the safety of supplements significantly differs in pregnant women, nursing mothers, children, and those with medical conditions or who are taking medications.
What is the right dosage for Quercetin?
Usually, dosages of Quercetin used range from 500–1,000 mg per day. However, some recommendations vary in the range of 12.5 to 25mg per kg body weight, which equals up to 2,000mg daily consumption of Quercetin when in isolation. However, there is not enough evidence to know if such an amount is safe for long-term use.
If taken on its own, Quercetin has quite a low bioavailability, which means the body absorbs it poorly. Therefore, some supplements may include other compounds, such as vitamin C or Bromelain, that increase quercetin absorption.
Sometimes, it is suggested to combine it with other flavonoids such as Resveratrol or green tea catechins, which may increase the potency and get the benefits at a lower level of intake.
The appropriate dosage for your condition depends on personal factors, including your age, gender, and medical history. Follow the recommendations on product labels and consult your pharmacist or healthcare provider if you plan to take this supplement.
Top-5 Quercetin products
Quercetin as a supplement comes in various forms, mostly as capsules with different content. Here are the top 5 of the most popular quercetin products:
Quercetin Dihydrate Powder
Quercetin Dihydrate acts as a powerful antioxidant and a flavonol that may promote healthy respiratory function, support heart, kidneys and prostate health, maintain healthy metabolic function, and help to fortify immune function. Quercetin Dihydrate doesn’t contain any other ingredients.
Optimised Quercetin
It is a mix of Quercetin with fruit and veggies extracts, such as apples and onions. Such a combination strengthens properties of each ingredient, and additional vitamins help to support a healthy immune response. The most common dosages are 250mg and 500mg per capsule.
Quercetin with Bromelain
Bromelain is a protein-digesting enzyme found in pineapple stems. As it also supports healthy immune system function, the combination of Quercetin and Bromelain provides powerful immunomodulating benefits important to handle occasional seasonal discomforts, such as allergies, nasal congestion or eczema. Quercetin with Bromelain also acts as a digestive enzyme and antioxidant, reducing damage to the digestive system and improving digestion.
Taking them together is a smart move as they enhance each other’s anti-inflammatory actions. Besides, Bromelain may increase the absorption of Quercetin into the bloodstream.
Quercetin with Resveratrol
Resveratrol is a polyphenol, found in the skin of red grapes, berries and peanuts. It is promoted as an alternative to red wine. Some studies suggest that Resveratrol may support heart health, protect nerve cells from damage, and prevent ageing processes. Both compounds are thought to have antioxidant properties.
Eye vitamins
That is a mix of Lutein, Zeaxanthin, Quercetin, Vitamin A and other beneficial ingredients. Such a combination not only provides your body with essential nutrition from a healthy diet but also helps to preserve eye health, maintain good eyesight, provide nutrients for eye care, and provide support to the macula, lens, and other eye tissues.
Whatever you choose, it’s better to look for quercetin products free of artificial ingredients, potentially dangerous preservatives or GMOs. The best option is to buy your flavonoid superpower from GMP compliant facilities, subjected to strict third-party testing.
Anastasiia Myronenko
Anastasiia Myronenko is a Medical Physicist actively practicing in one of the leading cancer centers in Kyiv, Ukraine. She received her master’s degree in Medical Physics at Karazin Kharkiv National University and completed Biological Physics internship at GSI Helmholtz Centre for Heavy Ion Research, Germany. Anastasiia Myronenko specializes in radiation therapy and is a fellow of Ukrainian Association of Medical Physicists.