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Quercetin

& Michel Chrétien

As coronavirus spread speeds up, Montreal researchers will trial an anti-viral treatment for COVID-19 in China

Quercetin has already proven successful at treating Ebola and Zika viruses

Researchers in Québec are hopeful that a drug derived from plants could be the key to curing infections caused by the novel coronavirus.

The broad spectrum anti-viral medicine known as quercetin has already proven successful at treating Ebola and Zika viruses, says Dr. Michel Chrétien, a researcher at the Clinical Research Institute of Montreal.

Now, he and co-researcher Majambu Mbikay are awaiting approval to send the drug to China where a clinical trial will test its effectiveness on COVID-19.

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"As soon as we receive the OK from China, we are ready to move," Chrétien told The Current's Matt Galloway.

Since the COVID-19 outbreak first began in January, researchers around the world — including in Canada — have been racing to develop a vaccine or treatment for the illness.

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While Chrétien cautions against "false hope" saying that quercetin's effectiveness for treating COVID-19 must be proven, Mbikay is optimistic for its potential.

He believes the novel coronavirus may infect people in a way similar to viruses that came before it. That means the drug could have the ability to block the virus from developing in the body.

"We believe that this particular drug interrupts the entry of viruses … so that you can attack several viruses at the same time," said Mbikay.

China trials

Since the SARS outbreak in 2003, researchers have been studying potential treatments for the disease amid worries that it could resurface. As part of that research, Mbikay says, he and Chrétien stumbled upon quercetin. As of Friday, COVID-19 has infected people in 49 countries according to the WHO, with more new cases reported in South Korea than China where the disease originated.

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The Ontario government announced the province's 7th case of the illness on Friday, bringing the total of confirmed cases in Canada to 14.

Though the WHO has yet to declare the outbreak a pandemic, several countries and institutions are preparing the for possibility. 

Given the illness' rapid spread, Chrétien is hoping trials for the drug can will quickly confirm whether or not quercetin is effective for treating COVID-19 safely.

Based on the trial protocol he has developed with his team, 20 to 30 patients will be given the drug and monitored for reaction. The following week more will be added.

"Then you collect all the data — that clinical data — and then you make an evaluation on a weekly basis, if not daily basis, to see how it goes."

He says it's possible that they will have results on quercetin's ability to treat COVID-19 within 60 days of a clinical trial starting.

Chrétien says that they have requested funding from the federal government for a Canadian trial, they are waiting to hear back.

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Low cost

Some patients infected with COVID-19 are currently being treated with a variety of anti-viral drugs, some with a price tag upwards of $1,000 per injection, Mbikay says.

Quercetin, by comparison, would cost just $2 per day.

"It is not expensive. It's a natural product. It's found in nature and purified from plants. Compared to what is available now, and that is being tried in China right now, it doesn't compare in terms of price," Mbikay said.

Chrétien adds that quercetin is an oral drug, which provides benefits over intravenous anti-virals.

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As the novel coronavirus begins to infect people in developing countries, Mbikay adds that creating an affordable treatment is key to slowing the outbreak.

"If we can show that this quercetin works, it would be made available to African countries, [other] countries that do not have the infrastructure, nor the means to combat it effectively," he said.

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Written by Jason Vermes. Segment produced by Paul MacInnis.

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SOURCE= https://www.cbc.ca/radio/thecurrent/the-current-for-feb-28-2020-1.5479561/as-coronavirus-spread-speeds-up-montreal-researchers-will-trial-an-anti-viral-treatment-for-covid-19-in-china-1.5480134

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ANOTHER ARTICLE ON HIS WORK; https://www.mcgilltribune.com/sci-tech/montreal-researchers-propose-a-treatment-for-covid-19-170320/

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FROM MACLEANS

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MICHEL-CHRETIEN-CORONAVIRUS-810x608-1582

                            Fifteen years ago, a medical researcher named Michel Chrétien and his longtime collaborator Majambu Mbikay, a Congolese scientist, unhatched a theory in their Montreal laboratory. In the aftermath of the SARS epidemic that infected 8,000 patients in 26 countries, Chrétien and Mbikay, researchers at the Clinical Research Institute of Montreal (IRCM), began testing their idea that a derivative of quercetin, a plant compound known to help lower cholesterol and treat inflammatory disease—and common, at low doses, in over-the-counter medication—was a “broad spectrum” antiviral drug that could fight a range of viruses.

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When an Ebola outbreak struck West Africa in 2014, the two scientists teamed up with the National Microbiology Laboratory in Winnipeg to test quercetin’s effectiveness on mice infected with Ebola—and found it effective even when administered only minutes before infection. It still needs to undergo clinical trials.

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But when a new global health crisis erupted in Wuhan, China late last year, Chrétien and his team once again got to thinking. They believed the drug might work on COVID-19, which has infected more than 130,000 people and killed 4,700, according to the World Health Organization. They knew a Swiss drug manufacturer, Quercegen Pharmaceuticals, could rapidly produce doses of the treatment in the hundreds of thousands.

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The 84-year-old Chrétien was, for a time, the world’s seventh most cited scientist. His name runs atop more than 600 publications and he proudly affixes an Order of Canada pin to his lapel. His achievements rival those of his older brother Jean—an impressive claim given that particular sibling served as prime minister of Canada for a decade. Michel has almost certainly saved more lives in his time.

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Michel Chrétien has a long-standing connection to high-level scientists in China. While a student at the University of California, Berkeley, he received some training from a Chinese researcher, Dr. C.H. Li, an enduring connection that saw him visit and work in China eight times starting in 1979. In the 1980s, Chrétien was an honorary professor at the Chinese Academy of Medical Sciences and Peking Union Medical College. In 1984, when he started a decade-long stint as president of the IRCM, he trained emerging scientists from China there. One of those relative youngsters was Chen Zhu, a molecular biologist who, back home in China, eventually entered politics and served as minister of health from 2007 until 2013. When a novel coronavirus outbreak exploded in China this past January, Chrétien contacted Zhu with an offer: “Can we help?”

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Zhu contacted officials at the highest levels of the National Health Commission, the government agency managing the crisis. Word came back to Chrétien and his team in mid-February. Last week, they invited Chrétien’s team to start clinical trials in China. The plan: send samples of quercetin to the Chinese Academy of Sciences in Wuhan. The Canadian and Chinese scientists would collaborate on the trials, which would include about 1,000 test patients. Chrétien and Mbikay plan to join colleagues from the non-profit International Consortium of Antivirals—which Chrétien co-founded with Jeremy Carver in 2004 as a response to the SARS epidemic—in manning a 24/7 communications center as soon as clinical trials go ahead.

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The U.S.-based Food and Drug Administration has already approved quercetin as safe for human consumption, which means the researchers can skip testing on animals. If the treatment works, it’ll be readily available. Now Chrétien just needs the funding to start the trials. He estimates the teams need $5 million. But the payoff, he says, could be huge.

Chrétien’s team says their treatment would cost only $2 a day. They’ve spent weeks pursuing officials at Global Affairs Canada, including senior staff in the office of Foreign Minister Francois-Philippe Champagne. The Lazaridis Family Foundation has already contributed $1 million to the cause, enough to start clinical trials. There’s no time to waste, says Chrétien. “I’ve been doing science all my life. I’ve stumbled on things my entire career, and this is probably the most urgent one I’ve been confronted with,” he says.

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Quercetin isn’t the only possible treatment for COVID-19; Nature reported that 80 clinical trials on potential treatments are underway in China. But it remains one of the biggest potential leaps in finding a treatment for the deadly coronavirus strain; if it works, it could save thousands of lives.

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Chrétien, who has spent most of his extensive medical career wearing a lab coat and testing hypotheses, simply touts the benefits of academic freedom as he and his team go about their work. “Basic science is worth doing for the sake of doing it, not knowing what the results will be in the short term or medium term,” he says. “Long-term returns can be big.”

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SOURCE; https://www.macleans.ca/news/canada/a-made-in-canada-solution-to-the-coronavirus-outbreak/

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Biography of Michel Chrétien

  • IRCM Emeritus Research Professor 

  • Emeritus Professor, Université de Montréal

  • Emeritus Scientist, Chronic Disease Program, Ottawa Hospital Research Institute (OHRI)

  • Professor, Department of Biochemistry, Microbiology and Immunology (BMI), Faculty of Medicine, University of Ottawa

  • Founder and Professor, Ottawa Institute of Systems Biology (OISB)

Honorary Degrees

  • D.Sc. (Honoris Causa), Université de Liège, Belgium (1980)

  • D.Sc. (Honoris Causa), Université René Descartes, Paris (1992)

  • D.Sc. (Honoris Causa), Université Laurentienne, Ontario (1996)

  • D.Sc. (Honoris Causa), University of Guelph, Ontario (1999)

  • D.Sc. (Honoris Causa), Memorial University, Newfoundland and Labrador (2000)

Executive and Research Positions

  • Scientific Director and President, IRCM (1984-1994)

  • Scientific Director and President, Loeb Research Institute (LRI), Ottawa Hospital (1998-2001)

  • Laboratory Director, IRCM, LRI and OHRI (1967-present)

Degrees and Training

  • MD, Université de Montréal (1960)

  • M.Sc., Experimental Medicine (Drs. J Genest/JSL Browne), McGill University  (1962)

  • MRC Research Fellow (Dr. J Genest), Hôtel-Dieu de Montréal (1960-1962)

  • Resident, Internal Medicine and Endocrinology (Drs. G Thorn/G Cahill), Harvard Medical School (1962-1964)

  • Assistant Biochemist (Dr. CH Li), UC Berkeley and UCSF (1964-1967)

  • Professor in residence (sabbatical), Un Cambridge (Dr. L Iversen) & Salk Institute (Dr. R Guillemin) (1979-1980)

Major Awards/Recognitions                                                                                

  • Fellow, Royal Society (London) (FRS)

  • Fellow, Royal Society of Canada (FRSC)

  • Fellow, American Association for the Advancement of Science (FAAAS)

  • Fellow, Royal College of Physicians and Surgeons of Canada (FRCPC)

  • Fellow, American College of Physicians (FACP)

  • Honorary Professor, Chinese Academy of Medical Sciences and Peking Union Medical College (PUMC)

  • Officer, Order of Canada (O.C.)

  • Officer, Ordre National du Québec (O.Q.)

  • Officer, National Order of the Legion of Honour, France (OLH)

  • Killam Prize, Art Council of Canada

  • McLaughlin Medal, Royal Society of Canada

  • Arthur Wynne Award, Canadian Society for Biomolecular Sciences

  • Boehringer-Mannheim Award, Canadian Society for Biomolecular Sciences

  • Henry Friesen Award, Royal College of Physicians and Surgeons of Canada

  • Clarke Institute of Psychiatry Prize, Toronto

  • Prix Archambault, ACFAS, Canada

  • Fuller Albright Medal, Peripatetic Club, USA

  • Jeremiah Metzger Lecturer, Am. Clin. Climatological Association, USA

  • Scholar, Josiah Macy Jr. Foundation, USA

  • Scholar, Jane Coffin Childs Memorial Fund for Medical Research, USA

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Source; https://ircm.qc.ca/en/biography/michel-chretien

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This woman is SOOOO much in resonance with what i too feel and i LUVLUVLUV her way of explaining this super awesome supplement. THIS IS NOT JUST A WIDE SPECTRUM ANTIVIRAL... it is to some a lifesaver for many many people...here she just is hitting the highlights so you can see i am not just boosting this for one reason albeit the virus is the current storm we are processing, and is the most immediate cause for needing Quercetin, Her presentation just NAILS IT.  She is located in the States sadly otherwise we might have become good friends. we all are in this together, so you can tell by her talk just how much this Quercetin can transform our lives, not just during this emergency. next is a small gallery with Quercetin info pics.

Quercetin and Immune Health taken directly from Metagenics Institute. we use Metagenics in treatment protocols.=

 

by Lewis Chang, PhD

Introduction

A quick search on ClinicalTrials.gov identified, as of this writing, 58 quercetin-related clinical intervention studies that are currently ongoing (19) or have been completed (39). Diverse health conditions, such as chronic obstructive pulmonary disease, type 2 diabetes, endothelial dysfunction, dyslipidemia, stroke, hepatitis C, acid reflux, inflammation, and oxidative stress, are the subject of interest. And in recent days quercetin’s role in immune health is getting a lot of attention as well. So what exactly is quercetin, where is it from, and what biological properties does it have that have attracted researchers’ attention?

Humans have had a long history of discovering remedies from plants. Dietary flavonoids are a large family of plant compounds sharing a polyphenolic structure and can be categorized into six major subfamilies: anthocyanidins, flavan-3-ols, flavanones, flavones, flavonols, and isoflavones.1

Dietary sources and intake

Quercetin is one of the better known flavonoids from the flavanol subfamily.1 The main dietary sources of quercetin for humans are apples, berries, capers, onions, tomatoes, kale, broccoli, nuts, buckwheat and tea.1  How much dietary quercetin (or flavonols) do humans consume? One study involving US health professionals reported a mean flavanol intake of 20 mg per day; about 75% of the total was quercetin.2 Data from a group of nurses in the US revealed an average intake of 15.4 mg quercetin per day.3 However, human consumption behavior is very complex; we are not eating the same things day after day. Some individuals may consume as much as 77 mg per day dietary quercetin, while others consume as little as 1 mg per day.4 The way food is prepared (boiling, frying, etc., can lower the bioavailability) and stored can also have an impact on quercetin concentration. This means many people are not getting the health benefits of quercetin.

 

 

 

Anti-inflammatory and antioxidative properties

A major health benefit of quercetin comes from its antioxidant (antioxidative) and anti-inflammatory properties.5 Inflammation is an essential immune response when facing pathogens (e.g., virus, bacteria, and fungus) or dangers (e.g., tissue damage caused by free radicals, cholesterol, amyloid beta, or asbestos). One of the major innate defense mechanisms is the activation of NLRP3 inflammasome (protein complexes in the cell that can sense signals from pathogens or dangers), leading to production of IL-1β, an important compound that mediates many aspects of inflammatory responses.6 However, dysregulated activations of inflammasome have been linked to initiation and progression of immune and inflammatory disorders such as atherosclerosis, inflammatory diseases, type 2 diabetes, autoimmune diseases, Alzheimer’s disease, and obesity, as well as collateral tissue damages that occur during infections.6,7 Quercetin has been shown to modulate NLRP3 inflammasome. In several experimental models of inflammatory conditions (including infections), quercetin reduced the production of reactive oxygen species and inhibited the overexpression of different components of NLRP3 inflammasome, resulting in reduced activation of NLRP3 inflammasome and leading to decreased secretion of IL-1β.8,9

Quercetin can also neutralize reactive oxygen species that are known to increase ER stress and mitochondrial dysfunction, both of which can activate NLRP3 inflammasome.10,11 Further, quercetin suppresses NF-κB pathway that also leads to reduced activation of NLRP3 inflammasome and productions of proinflammatory cytokines.12 These data demonstrate quercetin’s involvement in multiple pathways leading to modulation of NLRP3 inflammasome and reduction of downstream proinflammatory cytokine levels.

Other researchers have also discovered quercetin’s role in regulating immunity. For example,

  • Quercetin reduced TNF-α production in macrophages and lung epithelial cells when stimulated by LPS, an endotoxin found in bacteria that triggers immune response.13,14 This suggests quercetin modulates TNF-α-mediated induction of inflammatory cascades.

  • Quercetin exhibited a regulatory effect on several properties of immune cells such as inhibiting histamine and cytokine release from mast cells and inducing gene expression and production of Th-1-derived interferon (IFN)-g, as well as downregulating Th-2-derived IL-4 production by normal peripheral blood mononuclear cells.15,16 This suggests quercetin may have antiallergic properties.

  • Quercetin inhibited cells from being infected with influenza virus, Zika virus, and Ebola virus via interaction with viral hemagglutinin protein, inhibited virus entry into the cell, or reduced virus replication.17-19 This suggests quercetin has antiviral properties.

The antioxidant and anti-inflammatory as well as immunomodulatory properties of quercetin have inspired researchers to investigate its clinical effects. Quercetin supplementation at ≥ 500 mg/day significantly reduced fasting plasma glucose among patients with metabolic syndrome and related disorders,20 showed a small but significant reducing effect in circulating C-reactive protein levels,21 and significantly reduced blood pressure in cohorts largely made up of normotensive individuals.22 Also, a higher dose of quercetin has been shown to reduce upper respiratory tract infection severity and sick days in older adults.23

Summary

Naturally, more clinical investigation is greatly needed to fully understand quercetin’s clinical application in immune health and various inflammatory conditions. Nevertheless, with so much researchers have learned regarding quercetin and its beneficial biological properties, the future research direction of quercetin looks very promising.

Citations

  1. Panche AN et al. Flavonoids: an overview. J Nutr Sci. 2016;5:e47.

  2. Sampson L et al. Flavonol and flavone intakes in US health professionals. J Am Diet Assoc. 2002;102:1414-1420.

  3. Lin J et al. Dietary intakes of flavonols and flavones and coronary heart disease in US women. Am J Epidemiol. 2007;165:1305-1313.

  4. Cassidy A et al. Higher dietary anthocyanin and flavonol intakes are associated with anti-inflammatory effects in a population of US adults. Am J Clin Nutr. 2015;102:172-181.

  5. Anand David AV et al. Overviews of biological importance of quercetin: a bioactive flavonoid. Pharmacogn Rev. 2016;10:84-89.

  6. Guo H et al. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med. 2015;21:677-687.

  7. Chen IY et al. Response of host inflammasomes to viral infection. Trends Microbiol. 2015;23:55-63.

  8. Wang C et al. Quercetin and allopurinol ameliorate kidney injury in STZ-treated rats with regulation of renal NLRP3 inflammasome activation and lipid accumulation. PLoS One. 2012;7:e38285.

  9. Hu QH et al. Allopurinol, quercetin and rutin ameliorate renal NLRP3 inflammasome activation and lipid accumulation in fructose-fed rats. Biochem Pharmacol. 2012;84:113-125.

  10. Wang W et al. Quercetin and allopurinol reduce liver thioredoxin-interacting protein to alleviate inflammation and lipid accumulation in diabetic rats. Br J Pharmacol. 2013;169:1352-1371.

  11. Jiang W et al. Quercetin suppresses NLRP3 inflammasome activation and attenuates histopathology in a rat model of spinal cord injury. Spinal Cord. 2016;54:592-596.

  12. Zhang QY et al. Quercetin inhibits AMPK/TXNIP activation and reduces inflammatory lesions to improve insulin signaling defect in the hypothalamus of high fructose-fed rats. J Nutr Biochem. 2014;25:420-428.

  13. Manjeet KR et al. Quercetin inhibits LPS-induced nitric oxide and tumor necrosis factor-alpha production in murine macrophages. Int J Immunopharmacol. 1999;21:435-443.

  14. Huang R et al. Quercetin protects against lipopolysaccharide-induced acute lung injury in rats through suppression of inflammation and oxidative stress. Arch Med Sci. 2015;11:427-432.

  15. Nair MP et al. The flavonoid, quercetin, differentially regulates Th-1 (IFNgamma) and Th-2 (IL4) cytokine gene expression by normal peripheral blood mononuclear cells. Biochim Biophys Acta. 2002;1593:29-36.

  16. Kimata M et al. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clin Exp Allergy. 2000;30:501-508.

  17. Wu W et al. Quercetin as an antiviral agent inhibits influenza A virus (IAV) entry. Viruses. 2015;8.

  18. Wong G et al. Antiviral activity of quercetin-3-beta-O-D-glucoside against Zika virus infection. Virol Sin. 2017;32:545-547.

  19. Qiu X et al. Prophylactic efficacy of quercetin 3-beta-O-d-glucoside against Ebola virus infection. Antimicrob Agents Chemother. 2016;60:5182-5188.

  20. Ostadmohammadi V et al. Effects of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials. Phytother Res. 2019;33:1330-1340.

  21. Mohammadi-Sartang M et al. Effects of supplementation with quercetin on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2017;71:1033-1039.

  22. Serban MC et al. Effects of quercetin on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2016;5.

  23. Heinz SA et al. Quercetin supplementation and upper respiratory tract infection: A randomized community clinical trial. Pharmacol Res. 2010;62:237-242.

 

Lewis Chang, PhD is Scientific Editorial Manager of R&D at Metagenics. Dr. Chang received his PhD in Nutritional Sciences at University of Washington, along with his MS in Nutrition and Public Health from Teachers College, Columbia University and BS in Pharmacy from National Taiwan University. Prior to joining Metagenics, he conducted dissertation research and completed a research assistantship and postdoctoral fellowship at the Fred Hutchinson Cancer Research Center in Seattle, WA. Dr. Chang has authored or co-authored and managed the publication of over 30 peer-reviewed journal articles and numerous scientific abstracts and posters. He has quite a green thumb, enjoys opera, theater and jazz, and loves cooking, collecting art, and learning to play gypsy jazz guitar.

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