Quercetin, chemical name 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one or 3,30,40,5,7 pentahydroxyflavone, is classified as a flavonol, one of the six subcategories of flavonoid compounds. Quercetin is one of the most important plant molecules, with antioxidant, antiatopic, pro-metabolic, antiinflammatory, antiviral, and immunoprotective effects. Therefore, the beneficial actions of quercetin with respect to long-COVID have been discussed in numerous studies.
Nobel Prize winner Szent-Gyorgyi discovered both ascorbic acid (vitamin C) and the flavonoid quercetin (at that time labeled vitamin P). “Quercetin” derives from the Latin word “quercetum,” which means “oak forest,” and as a flavonol, is not produced in the human body. Quercetin is found in various vegetables and fruits, such as berries, lovage, capers, cilantro, dill, apples, and onions, where it is conjugated with residual sugars to form quercetin glycosides. It is yellow in colour and completely soluble in lipids and alcohol, insoluble in cold water, and sparingly soluble in hot water.
It should be noted that quercetin is completely soluble in lipids and alcohol, insoluble in cold water, and sparingly soluble in hot water.
About the studies
Quercetin acts as a free radical scavenger. Both in vitro and in vivo studies imply that quercetin is a potent antioxidant. The significant longstanding interest in the antiinflammatory activity of quercetin is secondary to quercetin’s free radical scavenging capacity and other diverse roles.
The other effects of quercetin include inhibition of platelet aggregation, inhibition of lipid peroxidation, inhibition of pro-inflammatory mediators such as lipoxygenase and phospholipase A2, prevention of capillary permeability, and enhancement of mitochondrial biogenesis.
Quercetin has been studied in various types and models of viral infection due to its promising antiviral effects such as the inhibition of polymerases, proteases, reverse transcriptase, the suppression of DNA gyrase, and binding of viral capsid proteins.
A large body of evidence has confirmed that quercetin and its derivatives have antiviral effects against influenza A virus, Respiratory syncytial virus, Rhinovirus.
The evidence pointed to plausible anti-SARS-CoV-2 mechanisms which include:
a) Quercetin protects against infection by preventing viral entry into host cells. A recent study used computational docking model to identify small molecules capable of binding to either the isolated viral spike protein at its host receptor binding region or to the spike protein/human angiotensin-converting enzyme 2 receptor (ACE2) interface, to potentially limit host cell viral recognition and/or to disrupt host–virus interactions. The results showed that quercetin was identified as one of the highest scored ligands in the spike protein/ACE2 receptor interface.
b) Quercetin represses replication inside cells by inhibiting 3C-like proteases, or activating the nuclear factor erythroid-derived 2-like 2 (NRF2) pathway.
Quercetin inhibits 3C-like proteases activity which is vital for coronavirus replication, including SARS-CoV-2. Also, quercetin activates the nuclear factor NRF2 pathway that transcriptionally upregulates a network of cytoprotective genes, including the antioxidant gene.
d) Quercetin has immunomodulatory properties, inhibiting nuclear factor kappa B, inflammasome, and interleukin-6-driven cytokine release.
e) Quercetin mitigates thrombotic events by the potent inhibition of protein disulfide isomerase, an enzyme involved in the formation of platelet-mediated thrombin at the site of vascular injury.
There is evidence that co-administration of vitamin C and quercetin can enhance therapeutic effects and antiviral properties of quercetin. Co-administration of vitamin C and quercetin have a synergistic antiviral activity due to overlapping antiviral and immunomodulatory properties. Also, ascorbate have the capacity to recycle quercetin, making it more effective.
Also. the combination of quercetin and the structurally related flavone luteolin can provide additional benefits, especially when formulated with olive pomace oil which increases oral absorption which is otherwise very limited (<10%).