The structures of the two most abundant quercetin conjugates found in the blood after oral consumption of quercetin [6] , [7] , [9] are shown to illustrate that the bulky attached moieties would preclude binding to the same site as quercetin. Quercetin O -glucoside is also shown as the major form of quercetin in onions [19] before digestion, which has a bulky glucose moiety attached.
The crystal structure between ACE2 and the viral spike protein has recently been refined [20]. For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.
For a solution of quercetin to be active, a target of at least three times the inhibition constant is reasonable at the site of interaction, i. These points highlight that if any clinical studies were to be conducted to harness the in silico and in vitro data, the delivery method of the bioactive molecule is of critical importance. The United States Food and Drug Administration has already approved oral doses of quercetin as safe for human consumption.
Quercetin given nasally was effective in a rat model of allergic rhinitis [12] , and the safety of quercetin has been favourably assessed [13]. Quercetin at high doses, like any other bioactive compound, could have potentially off-target effects.
Following local application by a nasal spray the possibility exists that quercetin could be transported or diffuse to other tissues such as the lungs and blood. Previously found beneficial effects on cardiovascular health biomarkers after regular consumption of quercetin [14] could deliver an additional positive outcome. Patients with pre-existing cardiometabolic syndromes such as hypertension are at increased risk during Covid infection, and the protective effects of quercetin increase the justification for trials.
However, quercetin treatment should be cautioned in the case of pre-existing lung cancer. Although many of the effects of quercetin were beneficial in that setting, the fact that quercetin can reprogram cellular energy metabolism should be taken into account [15] , [16]. We have recently published a review which traces the history of research on quercetin and other flavonoids [17]. One study on Covid and quercetin has so far been entered into www. We encourage researchers to consider bioavailability issues before embarking on expensive clinical trials.
Based on the evidence presented here, it is possible that a nasal spray of dilute quercetin in a suitable vehicle, administered regularly at low doses during the early stages of infection, could attenuate entry of the virus into cells and so halt progress of the infection, possibly leading to a reduced need for hospitalisation.
We suggest that clinical trials should be conducted in a timely fashion to test this. However, we emphasize that oral administration of even high doses of quercetin, either as a drug in pure form or in food, is unlikely to be successful owing to the known metabolism of quercetin, involving extensive conjugation and leading to low plasma concentrations of free quercetin.
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. National Center for Biotechnology Information , U. Biochem Pharmacol. Published online Jun Author information Article notes Copyright and License information Disclaimer.
Gary Williamson: ude. All rights reserved. Elsevier hereby grants permission to make all its COVIDrelated research that is available on the COVID resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. This article has been cited by other articles in PMC.
Graphical abstract. Open in a separate window. Abstract Commonly used drugs for treating many conditions are either natural products or derivatives.
Bioavailability A key aspect of the therapeutically successful action of any drug is delivery to the appropriate site of action. Doses required For a solution of quercetin to be active, a target of at least three times the inhibition constant is reasonable at the site of interaction, i. Recommendations We encourage researchers to consider bioavailability issues before embarking on expensive clinical trials.
November 17, November 16, Wendy J. Weber, N. What is the difference between the two FOAs? The R61 phase will support studies to: Demonstrate whether the natural product can produce a measurable biological signature related to the potential mechanism of action when given to humans, or Demonstrate bioavailability and collect short-term pharmacokinetic or pharmacodynamics data.
The R33 phase will support studies to: Demonstrate whether the biological signature measured in the R61 can be replicated in a second human study, Assess the association between the degree of impact on the biological signature and functional or clinical outcomes in a patient population, Collect pharmacokinetic or pharmacodynamics data to assure proper dosing of the products, or Determine the optimal dose of the natural product for use in a future efficacy study based on impact on optimizing the impact on the biological signature.
The second FOA, PAR , would be useful for investigators who already have data to demonstrate that the specific natural product to be used in the study: Impacts the proposed biological signature when used by humans, and Is bioavailable in humans.
Are there any new requirements for the application? What are the high program priority areas for these FOAs? By clicking on the Accept All Cookies button, or by continuing to use our website, you consent to all cookies. Accept All Cookies. Close Privacy Overview This website uses cookies to improve your experience while you navigate through the website. Out of these cookies, the cookies that are categorized as necessary are stored on your browser as they are essential for the working of basic functionalities of the website.
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