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Regarding COVID-19 and hydroxychloroquine (HCQ), HCQ is known to increase pH in lysosomes by 1-2 orders of magnitude, and also results in lethal intracellular heme overload in parasites responsible for hemolytic diseases. Question is, if circulating levels of xanthine oxidase (XO) are also known to be increased in hemolytic diseases, if one considers the natural flavonoids Kaempferol, quercetin, or luteolin, which are known xanthine oxidase (XO) inhibitors, antivirals, and anti-oxidants, what would be different about pharmacology of natural XO inhibitors and HCQ?

Is HCQ an XO inhibitor because it results in heme overload in parasites? What about anti-oxidant properties of HCQ in terms of radical scavenging? There is no information supporting the notion that HCQ is an antiviral.

Sticking with hemolytic diseases, for which the goal is overload of intracellular heme in parasites, what would happen if a human took high levels of an XO inhibitor that wasn't HCQ during malaria?

XO inhibitors usually result in an overall decrease in uric acid, essentially rendering them as a natural supplement for gout -- i.e., replacement to allopurinol, which has horrendous side effects.

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HCQ does show antiviral properties in vitro, but, in vivo (in humans), when taken after an initial dose of 800mg for 4 days at 600 mg/day, it was not found to prevent COVID-19 in high-risk exposure settings. Thus, it didn't stop people from getting SARS-CoV-2 infection followed by onset of symptoms/severity.

I suspect this is exactly what would happen with flavonoids, many of which have shown antiviral properties in vitro (laboratory settings). The information on flavonoids and SARS-CoV (2003) is very sparse, but several flavonoids did inhibit SARS-CoV in vitro (see last paragraph below). I do know there was a clinical trial approved in 2020 by NIH in which the investigators received an IND (From FDA) to use diosmin as a supplement to treat patients with COVID-19 (i.e. hospitalized). However, I don't know if was completed. Diosmin is available OTC as a supplement, and used via prescription under the brand names Dafflon® and Vasculera® for chronic venous insufficiency (CVI), which is caused by venous hypertension (VH). VH, in turn, aggravates metabolic imbalances leading to a self perpetuating cycle of further metabolic changes, including venous acidosis. These changes promote further inflammation in vascular tissue leading to edema, skin damage and possible ulceration and deep vein thrombosis (DVT). Varicose veins and hemorrhoids are also part of the spectrum of CVI disorders.

Interestingly, it took 16 years before a group published the most comprehensive paper on in vitro inhibition if SARS-CoV (2003) by many flavonoids that were considered.