Pomegranate Peel/extract may help increase NAD+

Niacin supplementation may help when NAD+ is low during inflammatory conditions, which might include a viral infection or recovery. This topic was introduced in the recent post Kale & Carrots – super good right? maybe not for everyone. NAD+ levels also tend to be reduced with aging and may be a factor in chronic illness associated with aging. Promoting better NAD+ levels may help protect against aging and chronic illness associated with aging. “NAD+ levels decline during ageing, and alterations in NAD+ homeostasis can be found in virtually all age-related diseases, including neurodegeneration, diabetes and cancer. ” (3)

Providing niacin (6) and niacinamide would be helpful to promote more NAD+ as niacin can be made into the chemical. Preventing breakdown is another way to promote more NAD+. (3) EGCG was mentioned within the reference list of the Kale & Carrots post in some excerpts. EGCG may be able to promote more NAD+ within cells, and a few other flavonoid phytonutrients that may help reduce breakdown of NAD+ by inhibiting the enzymes involved in its metabolism. (7)

  • EGCG: “NMNATs are also attractive targets for raising NAD+ in cells because they have dual substrate specificity for NMN and nicotinic acid mononucleotide (NaMN), and they contribute to both de novo and salvage pathways (Zhou et al., 2002). The green tea compound epigallocatechin gallate [EGCG] has been reported to activate NMNAT2 by more than 100% and NMNAT3 by 42% at 50 mM, although this needs to be confirmed, as no data were presented in the paper (Berger et al., 2005).” (7)

Pomegranate peel/extract is also a source of EGCG. Pomegranate preparation tips and more information about health benefits is able on page effectivecare.info/G13. Pomegranate. It may have anti-inflammatory activity through down regulation of Fox03a (4) which is a protein that can increase oxidative stress damage in mitochondria (5) where the NAD+ chemical reactions are taking place.

  • Other phytonutrients may also be helpful to promote NAD+ by decreasing breakdown of it: “An alternative approach to raising NAD+ is to inhibit its degradation either by inhibiting PARPs or NADases, also known as glycohydrolases. The major NADase in mammals, CD38, is inhibited in vitro at low micromolar concentrations by flavonoids including luteolinidin, kuromanin, luteolin, quercetin, and apigenin (IC50 < 10 mM) .” (7)

Luteolinidin is an plant extract (a deoxyanthocyanidin) that is still in research phases for use as a CD38 inhibitor. (1) Kuromanin is also a plant extract, an anthocyanin, available for sale (expensive), under investigation as a CD38 inhibitor (preventing breakdown of NAD+) and neuro protectant. (2)

  • Luteolin is a flavonoid “found in celery, thyme, green peppers, and chamomile tea,” (18) and “chrysanthemum flowers, sweet bell [green/red/orange] peppers, carrots, onion leaves, broccoli, and parsley [78]. (21)
  • Quercetin – is in onions, garlic, green leafy veg, citrus peel, figs, and is a focus of several recent posts: Citrus Fig jam: (14), Hesperidin & quercetin content in citrus peel: (15), Decongestant properties of hesperidin/citrus peel: (16).
  • Apigenin is a flavonoid found in “grapefruit, plant-derived beverages and vegetables such as parsley, onions, oranges, tea, chamomile, wheat sprouts and in some seasonings.” (19) (Intake of more dietary flavonoids on average was associated with a reduced cancer risk. (19))
  • For references (14, 15,16, 18, 19, 21) see post: Phytonutrients that may help against SARS-CoV-2.

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

Reference List

  1. Luteolinidin chloride, medchemexpress.com, https://www.medchemexpress.com/luteolinidin-chloride.html
  2. Kuromanin chloride, goldbio.com, https://www.goldbio.com/product/4730/kuromani-chloride
  3. Katsyuba, E., Romani, M., Hofer, D. et al. NAD+ homeostasis in health and disease. Nat Metab 2, 9–31 (2020). https://doi.org/10.1038/s42255-019-0161-5 https://www.nature.com/articles/s42255-019-0161-5?proof=t
  4. Liu S, Zhang X, Sun M, Xu T and Wang A: FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity. Int J Mol Med 40: 175-181, 2017 https://www.spandidos-publications.com/10.3892/ijmm.2017.3003
  5. Tseng AH, Shieh SS, Wang DL. SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage. Free Radic Biol Med. 2013 Oct;63:222-34. doi: 10.1016/j.freeradbiomed.2013.05.002. Epub 2013 May 7. PMID: 23665396. https://pubmed.ncbi.nlm.nih.gov/23665396/
  6. Pirinen E, Auranen M, Khan NA, Brilhante V, Urho N, Pessia A, Hakkarainen A, Kuula J, Heinonen U, Schmidt MS, Haimilahti K, Piirilä P, Lundbom N, Taskinen MR, Brenner C, Velagapudi V, Pietiläinen KH, Suomalainen A. Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy. Cell Metab. 2020 Jun 2;31(6):1078-1090.e5. doi: 10.1016/j.cmet.2020.04.008. Epub 2020 May 7. Erratum in: Cell Metab. 2020 Jul 7;32(1):144. PMID: 32386566. https://pubmed.ncbi.nlm.nih.gov/32386566/

Pomegranate peel catechins – inhibition of NET formation

We could show that the flavonoids (−)-epicatechin, (+)-catechin hydrate, and rutin trihydrate as well as vitamin C and the pharmacological substances N-acetyl-L-cysteine and 5-aminosalicylic acid inhibited PMA induced ROS production and NET formation.” (1)

Why care about NET formation? because it may be associated with worse risk of coagulation and blood clots forming in severe COVID-19 illness. (3, 4) Interleuken-6 (IL-6) can increase NET formation by neutraphil white blood cells attempting to ensnare pathogens and IL-6 levels tend to be elevated in more severe COVID-19 illness.

NET-neutraphil extracellular traps: “Thrombosis [coagulation/blood clotting], sepsis, and thick mucous secretions share neutrophil extracellular traps as a common causal agent. In addition to phagocytosis and degranulation, neutrophils can kill pathogens by extruding neutrophil extracellular traps (NETs), a process termed NETosis.” (2)

Rutin is found in citrus peel and other plants. Epicatechin and catechin hydrate are in pomegranate peel or juice possibly (more in the peel). N-acetyl-L-cysteine is available as a supplement also known as NAC, and 5-aminosalicylic acid is a medication. Acetylsalicylic acid is aspirin and it also inhibits NET formation. (search results) Salicylic acid may be in some spices/plant foods. Many spices used in Indian cooking are good sources of salicylic acid. (post: Carrots, Spices, and baby aspirin help prevent cancer)

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

Reference List

  1. Kirchner T, Hermann E, Möller S, et al. Flavonoids and 5-aminosalicylic acid inhibit the formation of neutrophil extracellular traps. Mediators Inflamm. 2013;2013:710239. doi:10.1155/2013/710239 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871909/
  2. Yanuck SF, Pizzorno J, Messier H, Fitzgerald KN, Evidence Supporting a Phased Immuno-physiological Approach to COVID-19 From Prevention Through Recovery. athmjournal.com/ https://athmjournal.com/covid19/research/evidence-supporting-a-phased-immuno-physiological-approach-to-covid-19-from-prevention-through-recovery/ *”interventions for one phase may not be appropriate for a different phase. The 4 phases addressed are: Prevention, Infection, Inflammation & Recovery.
  3. Thierry AR, Roch B. SARS-CoV2 may evade innate immune response, causing uncontrolled neutrophil extracellular traps formation and multi-organ failure. Clin Sci (Lond). 2020 Jun 26;134(12):1295-1300. doi: 10.1042/CS20200531. PMID: 32543703. https://pubmed.ncbi.nlm.nih.gov/32543703/
  4. Julie Kiefer, Clues to COVID-19 Complications Come from NET-Like Inflammatory Response. Jun 29, 2020, healthcare.utah.edu, https://healthcare.utah.edu/publicaffairs/news/2020/06/nets-covid.php

Treatments vs ‘a cure’

The question of what is a treatment versus what is a cure has been an issue online, while writing and communicating about dietary foods, supplements, or medications that might help treat patients with SARS-CoV(2) – Coranovirus Disease 2019, or COVID-19. The definition of the words suggest that a treatment is anything that helps with management of symptoms of a chronic or acute/short term illness, while a cure – to be cured – is something that resolves an illness.

Addition: It is being recommended to the FDA to fast track approval for preventive, early treatment with zinc and an anti-malarial and an antibiotic that are fairly available and have a long history of use, so risks and dosing have been studied. “It’s important to note that HCQ, zinc, and azithromycin are very well understood drugs with clear safety profiles; they are widely available, generic, inexpensive, and can be scaled rapidly, including to the developing world, which would be expedited by US leadership in recommendations.” More is included in the second half of this post about the zinc and anti-malarial medication. See this document for the recommendation to the FDA: (Immediate Treatment for Early Stage SARS-CoV-2 Infections).

Many treatments might be used to help a person become cured of a curable illness – so every single person that has recovered from being ill with the viral COVID-19 infection can be said to have been cured – with whatever treatments they used at home or were provided in a health care setting. I was sick with an untested illness that included symptoms matching the description and time-frame of the current pandemic infection. Once blood serology tests for antibodies becomes more widely available I may be able to have confirmation that the illness I had was due to the SARS-CoV(2) virus, (2/20 suspected exposure, 2/28 symptoms began, recovery took weeks).

Symptoms for me, and many people, started with a couple days of headache, exhaustion, nausea, vomiting, hot and cold feverish chills, and diarrhea. I coped by not eating, even water was nauseating. I stayed hydrated by sipping small amounts of water with a tablespoon or two of lime juice in it. Lemon juice or apple cider vinegar would also have provided similar acidity to stomach acid – if even water is nauseated then there is a problem with stomach acidity.

Along with the diarrhea there was intestinal pain with eating. The only foods that were very soothing were oranges with the white pith part of the peel left on and bean soup or sweet potato made with hydrolyzable tannins from pomegranate peel or walnuts. See the post ACE2, Diarrhea, COVID19, – It gets complicated.

The nausea and vomiting for me only lasted a couple days, the diarrhea lasted longer, a week or so, and as that was improving my cough, sore throat and difficulty breathing worsened. The cough became non-productive which translated from medical jargon equals – sticky thick mucus that just couldn’t be coughed out. There was an urge to cough and it would get bad enough to become oxygen deprived and see ‘stars’ – those little sparkly specks of whatever your brain/eyes are doing when you get too low in oxygen or with a severe headache.

The oranges with white part of the peel left on were soothing to the digestive system and helped thin the sticky mucus, can’t cough anything out problem. Hot steamy soup also helped thin the too-thick mucus problem so I was able to cough and feel better instead of worse. I was also using chewable vitamin C tablets, 100 milligram, which I had on hand and typically take one a day. I was using an extra one or two a day during the worst of the coughing.

Self-care strategies using nutrients/phytonutrients in moderate doses are considered First Aid rather than a medical treatment. Vitamin C Infusion given intravenously in high doses provided by a medical professional would be considered a medical treatment while my use of a chewable Vitamin C tablet in a 100 milligram dose for a sore throat would be considered First Aid, based on a definition within an employment policy about Workman’s Compensation. (wisconsin.edu/Medical Treatment Beyond First Aid).

Vitamin C has a recommended daily minimum intake of 60 milligrams for non-pregnant adults and 100 milligrams is only slightly more. High dose intravenous treatments may provide 15 grams over the course of the day. Adverse reactions are rare and the treatment has been successful for improving survival rate in the case of sepsis shock which can involve an excess of cytokines.

Many herbal nutrients can help the body have an immune reaction that is enough to cope with an infection without becoming an overactive response that results in an excessive amount of cytokines to be produced. I may have been lucky in my recovery or it may have been aided by the variety of nutrients and phytonutrients that I take as supplements or within my diet in the form of nutrient dense foods – or citrus peel and pomegranate peel – not typically considered food but very edible when the outer layer is removed and the white inner part is eaten, or the outer layer is prepared so only small amounts are used.

Traditional Chinese Medicinals (TCM) are used in combinations and are thought to be more effective than the herbs would be used singly. Individualized care by a trained practitioner is recommended as with any other medical care. The herbs have also been studied for potential use as anti-inflammatory medications if an active phytonutrient can be identified. Corylin from Psoralea corylifolia L. (Fabaceae) an herb used in both TCM and Ayurveda traditional healing has been found to have immunomodulatory effects which means it can help the body have enough of an immune response but not an overactive sepsis response. (2)

A computer modeling of the genetic structure of the SARS-CoV(2) virus was compared to a database of western medicines and a database of Traditional Chinese Medicinal herbs for potential treatments. Different areas of viral replication or cell entry were identified as possible targets for therapeutic agents and the potential treatments identified from the databases were grouped by the mechanism of action. (3)

Going through the list suggested that my routine use of multiple herbs, nutrient supplements, and nutrient dense foods may have helped my recovery as I use several of the potential therapeutic agents including some with different mechanisms of action.

  • In the first section PLpro inhibitors, I used citrus peel daily which includes hesperidin and neohesperidin and L(+)-Ascorbic acid – vitamin C, (13): “hesperidin and neohesperidin…might be the potential 3CLpro inhibitors and could probably be used for treating SARS-CoV-2.” (3)
  • The section also includes Riboflavin-vitamin B2 which I take a high dose of as it is water soluble and not available singly in RDA doses;
  • Silybin- which I would have in my Milk Thistle supplement;
  • and “…epigallocatechin gallate, [EGCG]…exhibited high binding affinity to PLpro protein, suggesting the potential utility of these compounds in the treatment of SARS-CoV-2.” (3) I use EGCG daily within pomegranate peel and/or green tea. It can also act as a zinc ionophore when zinc is available. (11)
  • (–)- Rosmarinic acid – is found in rosemary, an anti-inflammatory herb that I use generously in cooking because of the pain relieving/anti-inflammatory properties.
  • In the second section, 3C-like main protease (3CLpro) inhibitors: I would have a metabolite of riboflavin, Flavin mononucleotide, from my high dose vitamin B2 supplement, and Lutein which is found in cooked kale and other produce. The citrus peel phytonutrients hesperidin and neohesperidin also have this mechanism of action and rosmarinic acid from rosemary.
  • In the third section, RNA-dependent RNA polymerase (RdRp) inhibitors: silybin, in Milk Thistle is included again.
  • In the fourth section, Helicase (Nsp13) inhibitors, the citrus peel phytonutrients hesperidin and neohespiridin are mentioned along with other plant flavanoids: “The natural products, such as many flavanoids from different sources (α-glucosyl hesperidin, hesperidin, rutin, quercetagetin 6-O-β-D-glucopyranoside and homovitexin), …showed high binding affinity to this target.” (3) Rutin is found in green and black tea and a few other foods. Quercetagetin… seems to be a form of quercetin, which also can act as a zinc ionophore, (11) and is in citrus peel. Homovitexin is also called isovitexin and is found in cannabis and flaxseed and in a few other foods. (4)
  • In the fifth section, Targets inhibiting virus structural proteins, flavonoids are included again, with hesperidin and neohesperidin from citrus peel in my diet and “licoflavonol from Glycyrrhiza uralensis” in my supplement of licorice root. “By superimposing the ACE2–RBD complex to the hesperidin–RBD complex, a distinct overlap of hesperidin with the interface of ACE2 could be observed (Fig. 6C), suggesting hesperidin may disrupt the interaction of ACE2 with RBD [the RBD section of the SPIKE protein]. ” (3)
  • The sixth section Targets inhibiting virulence factor did not include any herbals that I take or eat regularly.
  • The seventh section Targets blocking host specific receptor or enzymes included neohesperidin and hesperidin from Citrus aurantium again, the two phytonutrients are also in the peel of other citrus species. (5) “The natural products, such as phyllaemblicin G7 from Phyllanthus emblica, xanthones from the plants of Swertiagenus, neohesperidin and hesperidin from Citrus aurantium, exhibited potentially high binding affinity to ACE2 protein. ” (3)

Six out of seven sections – and multiple possible phytonutrients or nutrients within the different potential areas targeting the virus mode of entry into the human cell at the ACE2 receptor or the viral replication process – I am recovered, and my use of the white part of the orange peel may have helped in five of the seven targets of action. Is it a cure? I am cured, recovered, not on a ventilator. I did have to stop smoking medical marijuana because I could tell I was heading for needing an asthma inhaler but I continued to use edible sources of cannabis as it helps a variety of health issues for me. I also use a high dose of zinc and the quercetin in citrus peel and onions, and EGCG in pomegranate peel and green tea, are both zinc ionophores – meaning they act as transport carriers to get zinc into an infected cell where the zinc can disrupt viral replication.

To use a sports metaphor – I like to cover all my bases, and shortstop, and center field, left and right field too. The wonder of nutrients and phytonutrients is they tend to be very low risk, some may have risk of overdose but not typically.

Treatments, multiple treatments might help provide a ‘cure‘, which refers to a recovery from illness. The idea that one medication is all you need to be ‘cured‘ became more of an expectation after antibiotics were discovered – however microbes mutate and become resistant when one drug is used consistently – and then the drug is no longer a cure. Using multiple treatments, that target different aspects of a pathogen’s mode of infection and replication needs, may help prevent mutations that make a single ‘cure‘ obsolete due to the pathogen developing resistance to the drug.

Many treatments might be needed for the various stages and range of symptoms that can occur with the COVID19, SARS-CoV(2) virus. It is new, waiting for clinical trials isn’t very helpful for people who are already sick. Citrus peel is readily available in fresh fruit or in Middle Eastern groceries as whole dried limes or powdered dried lemon or lime, and in the Traditional Chinese Medicinal Chen Pi. The whole peel includes the more bitter and potent outer part of the peel. One to two teaspoons is a more typical dose of the TCM Chen Pi and it would be used with a few others. The TCM guidance for COVID19 included licorice and astragalus which I also use daily as a supplement.

The inner white part of the peel is milder in flavor, I have been using an entire orange daily, half in the morning and half in the evening. This is my story, which I’m sharing as an example. Food is a personal choice, and fairly safe compared to many medications.

An orange peeled so the white pith remains.
The orange zest layer of the orange peel can be trimmed to leave the white pith with the sweet orange wedges. It is a rich source of quercetin, hesperidin, neohespidin and vitamin C..

Best of health, and best of appetite to all. – Severe lack of appetite, and also loss of sense of smell and taste, can all be symptoms of zinc deficiency. The infection process can use up nutrients faster than during normal health. Providing extra nutrients may be needed to promote healing – is that just expensive urine or an inexpensive ‘cure‘. If the person recovers from an illness – then they are cured. Waiting for clinical trials when nontoxic inexpensive solutions might be sitting on the grocery shelf seems like a mistake that can cost unnecessary lives.

Zinc with the aid of Zinc Ionophores also disrupt Viral Replication.

Zinc also has antiviral properties. Once it is carried into a cell by a zinc ionophore, whether nontoxic quercetin, EGCG, (11, 12) or potentially toxic Chloroquine or Hydroxychloroquine, (10), then it disrupts viral replication (6) by the mechanism of action in the third section – RNA-dependent RNA polymerase (RdRp) (3) of the computer modeling article.

Chloroquine and Hydroxychloroquine preferentially collect in the lungs which helps increase potency with smaller doses, part of risk is due to the medications also collecting more in cells with melanin which include skin and eye cells – damage to the eyes can be a risk with large doses or extended us for years as a malaria or autoimmune disease treatment. People with cardiac problems may also be more at risk of adverse cardiac reactions. (7)

Low magnesium (hypmagnesemia) or low potassium (hypokalemia) blood levels can be an indicator of cardiac risk with the use of Chloroquine or Hydroxychloroquine. (7) Dietary consult (me) would include in a hospital chart note the reminder that low magnesium levels can cause a suppression of potassium levels and therefore correcting the low magnesium might improve the potassium level too, and help protect against the risk of adverse cardiac events. (8)

With poor intestinal absorption low magnesium can become an acute risk – sudden, short term, or it can be a problem with chronic intestinal malabsorption of magnesium. Topical sources of magnesium can be absorbed through hair follicle pores. Magnesium chloride in lotions or liquid can be applied to the skin, or a foot soak or a bath with Epsom Salt, magnesium sulfate, can also be a beneficial source of bioactive sulfate. Foot soak, approximately 40 minutes for me, 1 cup Epsom Salt in a large wastepaper basket size container where the lower legs will also be covered by the magnesium rich water. Bath, approximately 20 minutes for me, research based also, with 1-2 cups of Epsom salt in a half-full bathtub. (9)

Just because a treatment is low cost, readily available, low toxicity risk, and effective, does not mean it is bad, it may just be bad for someone’s profit margin. Quercetin is readily available in many foods, raw red onion it the best source, although citrus peel may not have been included as a typical ‘food’ source. (14, 17) EGCG supplements are available derived from green tea, pomegranate peel is also a very good source and pomegranate season may be just near the end of availability for southern hemisphere consumers. Powdered pomegranate peel may be available in limited amounts. Citrus peel is readily available as fresh or dried products. Epsom salt is available in drugstores and the pharmacy section of department stores.

There has been some controversy in the US regarding use of chloroquine or hydroxychloroquine for treatment of patients with COVID19 infections. Supply issues can be resolved with increased production. The medication is also used for autoimmune patients (18) (who might be able to use artemisinin instead (15) or pomegranate peel (16), but ideally provide the pomegranate peel with zinc also, (11, 12) ) and there has been some trouble with filling their prescriptions due to an increase in demand due to the COVID19 epidemic. Production can be increased, the cardiac risk might be able to be reduced if topical sources of magnesium are provided to patients.

Whether the dose used is enough for effective control of viral replication is the theme of pdf presentation. Too low a dose may have been used in clinical trials that didn’t show efficacy for COVID19 treatment. Tere is a narrow range before toxicity is reached. Having a larger loading dose followed by smaller daily doses broken up into several small doses may be safer, while providing enough to be effective against the viral infection. (7) My big question would be – how much zinc was provided to patients in those trials? The pdf (7) never mentions zinc at all — while the chloroquines may also have some other antiviral capability, they have been shown to be effective against malaria when zinc is present in almost an equal weight to the chloroquine dose. (19)

Returning to my own health story – I do take a high dose zinc supplement for suspected pyroluria symptoms (might be genetic condition affecting an enzyme that would preserve the body supply of zinc and vitamin B6) and I did have more severe muscle cramps as part of my symptoms which is fairly normal for me and Epsom salt baths or footsoaks every 5-7 days helps to prevent or resolve the muscle cramps. Some individuals or conditions may cause long term problems with absorption of magnesium from the diet, or due to increased urinary loss of magnesium. Illness can increase need for magnesium as well as possibly decreasing absorption and increasing loss in sweating more, due to a high fever, or in urinary losses.

The heart is a muscle and all types of muscle use calcium to contract and magnesium to relax. Magnesium is given intravenously as a treatment for the long QT interval/Torsades de Pointes tachycardia that can be a cardiac adverse reaction with chloroquine treatment. (20) Why not give magnesium in a footsoak, before having a dangerous cardiac reaction?

Quercetin plus zinc has FDA approval for use in treatment of COVID19, Canadian research team.

  • CBC News Interview with “Dr. Michel Chrétien’s team at the Clinical Research Institute of Montreal” : Canadian team invited to do clinical trials in China for antiviral drug. *Quercetin deriviative plus zinc given 3-4 times per day, I hven’t found any results online yet. Feb 28, 2020, (youtube).

Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

Reference List

  1. Medical Treatment Beyond First Aid, wisconsin.edu,
  2. Hung, Y., Fang, S., Wang, S. et al. Corylin protects LPS-induced sepsis and attenuates LPS-induced inflammatory response. Sci Rep7, 46299 (2017). https://doi.org/10.1038/srep46299 https://www.nature.com/articles/srep46299
  3. Canrong Wu, Yang Liu, Yueying Yang, et al., Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B, 27 February 2020, https://doi.org/10.1016/j.apsb.2020.02.008 https://www.sciencedirect.com/science/article/pii/S2211383520302999 * the genetic structure of the SARS-CoV(2) virus more closely matches the first, 2003, SARS-CoV virus in the way it can enter at ACE2 Receptors than it resembles the genetic structure of the coronavirus from bats native to China. There has also not been research support of the theory that the bat virus can infect humans as the shape does not fit the human ACE2 receptor: “…4 among the 5 most important amino acids (L465, L495, Y502, D510, and H514) that bind to ACE2 12 in Bat-CoV RaTG13 differ from SARS-CoV-2 (Fig. 3C). And there is no related research literature about whether Bat-CoV RaTG13 can infect human yet.”
  4. Showing Compound Isovitexin (FDB000614), Foodb.ca, https://foodb.ca/compounds/FDB000614
  5. Rhyu, Meera & Kim, Eun-Young & Bae, In Young & Park, Yong-Kon. (2002). Contents of Naringin, Hesperidin and Neohesperidin in Premature Korean Citrus Fruits. Korean Journal of Food Science and Technology. 34. https://www.researchgate.net/publication/263398834_Contents_of_Naringin_Hesperidin_and_Neohesperidin_in_Premature_Korean_Citrus_Fruits
  6. Aartjan J. W. te Velthuis, Sjoerd H. E. van den Worm, Amy C. Sims, et al., Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture. PLOS Pathogens, Nov. 4, 2010, https://doi.org/10.1371/journal.ppat.1001176 https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1001176
  7. Umer, PDF about dosing and safety risks of the medications chloroquine and hydroxychloroquine.  Hypokalemia and hypomagnesemia can increase risks of cardiac side effects – Epsom salt foot soaks might be helpful, hypokalemia can be due to low magnesium availability in addition to low potassium intake or other metabolic imbalance due to hormones.  https://drive.google.com/file/d/19T-QIaE6FT-PzfWcnbTr5g6ZnV34WcL2/view?usp=drivesdk 
  8. Hypomagnesemia, MedicalNewsToday.com, https://www.medicalnewstoday.com/articles/321735
  9. J. Depew, Epsom salt footsoaks, Feb. 19, 2019, transcendingsquare.com, https://transcendingsquare.com/2019/02/19/epsom-salt-footsoaks/
  10. Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding W-Q (2014) Chloroquine Is a Zinc Ionophore. PLoS ONE 9(10): e109180. https://doi.org/10.1371/journal.pone.0109180 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109180
  11. Dabbagh-Bazarbachi H, Clergeaud G, Quesada IM, et al., Zinc ionophore activity of quercetin and epigallocatechin-gallate: from Hepa 1-6 cells to a liposome model. J Agric Food Chem. 2014 Aug 13;62(32):8085-93. doi: 10.1021/jf5014633. Epub 2014 Jul 31. https://www.ncbi.nlm.nih.gov/pubmed/25050823
  12. Houston DMJ, Bugert JJ, Denyer SP, Heard CM. Potentiated virucidal activity of pomegranate rind extract (PRE) and punicalagin against Herpes simplex virus (HSV) when co-administered with zinc (II) ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV [published correction appears in PLoS One. 2017 Nov 20;12 (11):e0188609]. PLoS One. 2017;12(6):e0179291. Published 2017 Jun 30. doi:10.1371/journal.pone.0179291 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493292/
  13. Shafiya Rafiqa, Rajkumari Kaula, S.A. Sofia, et al., Citrus peel as a source of functional ingredient: A review. J of the Saudi Society of Ag Sci, 17;4, Oct. 2018, pp 351-358 https://www.sciencedirect.com/science/article/pii/S1658077X16300960
  14. Quercetin, Pharmacology, Toxicology and Pharmaceutical Science/Quercetin, ScienceDirect.com, https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/quercetin
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  1. Vitamin C Is an Essential Factor on the Anti-viral Immune Responses through the Production of Interferon-α/β at the Initial Stage of Influenza A Virus (H3N2) Infection https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659258/
  2. Sy Mukherjee, China’s high smoking rate may be exacerbating the coronavirus outbreak,  Feb. 19, 2020, Forbes.com, https://www.google.com/amp/s/fortune.com/2020/02/19/coronavirus-china-smoking-rate-men/amp/