Quercetin — A Natural Alternative to Hydroxychloroquine

• December 27, 2021

Full article: https://covid19.onedaymd.com/2021/12/quercetin-natural-alternative-to.html

Quercetin Against SARS-CoV-2

In Part 2 of the anthology, Modern Discontent reviews the evidence behind the recommendation to use quercetin against COVID-19 specifically. As mentioned, zinc has antiviral activity, and quercetin helps shuttle the zinc into the cell. But quercetin also has other mechanisms of action that make it useful in the fight against COVID-19.

Quercetin modulates NLRP3 inflammasome, an immune system component involved in the uncontrolled release of proinflammatory cytokines that occurs during a cytokine storm.

For example, quercetin has been shown to:

Inhibit SARS-CoV-2 spike protein to ACE2 receptor docking.5,6,7 Computational modeling studies have shown quercetin can bind to the ACE2 receptor and the spike protein interface, thereby inhibiting the two from binding together. By preventing viral attachment, it helps prevent viral entry into the cell. Commenting on one of these studies, Modern Discontent notes:8

“Although [a] computer modeled study,9 the evidence here suggests that quercetin’s binding activity to ACE2 is comparable to other standard of care drugs used to treat SARS-CoV-2 (eg. Remdesivir, Lopinavir, Ritonavir).”

Inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF-α) production in macrophages.10 (TNF-α is a cytokine involved in systemic inflammation, secreted by activated macrophages, a type of immune cell that digests foreign substances, microbes and other harmful or damaged components.)

Inhibit the release of proinflammatory cytokines and histamine by modulating calcium influx into the cell.11

Stabilize mast cells and regulate the basic functional properties of immune cells, thereby allowing it to inhibit “a huge panoply of molecular targets in the micromolar concentration range, either by down-regulating or suppressing many inflammatory pathways and functions.”12

Act as a zinc ionophore, i.e., a compound that shuttles zinc into your cells.13 This is one of the mechanisms that can account for the effectiveness seen with hydroxychloroquine, which is also a zinc ionophore.

Boost interferon response to viruses, including SARS-CoV-2, by inhibiting the expression of casein kinase II (CK2)14 — CK2 is an enzyme that is fundamental to controlling homeostasis at the cellular level. There is evidence that it down-regulates the ability a cell has to generate Type 1 interferon when attacked by a virus.

It does this by inhibiting retinoic acid-inducible gene I (RIG-I),15 which has protein sensors that signal genetic expression of type 1 interferon by identifying the replication of RNA viruses, such as SARS-CoV-2. Quercetin inhibits the expression of CK2, which slows the replication of RNA viruses.16

Interferons are a subset of cytokines discovered in 1957.17 These cells are often the initial defense against viruses. There are two types and three forms of interferon. Within Type 1 interferon, there are alpha and beta. Type 2 interferon has the gamma form.18

The different types are based on the function of the cytokine. Type 1 interferons help cells resist viruses. Type 2 aids in responding to infections and cancer growth. The name "interferon" came from the ability of Type 1 to interfere with the virus's ability to duplicate. A cell secretes interferons when a foreign substance, like a virus, is detected.

However, the interferon does not function by attacking the virus. Instead, it tells the infected cell and the cells that surround the infected cell to make proteins that stop viral replication. In a nutshell, quercetin stops CK2 from interfering with the action of Type 1 interferon so cells receive the signal to stop viral replication.

Modulate NLRP3 inflammasome, an immune system component involved in the uncontrolled release of proinflammatory cytokines that occurs during a cytokine storm.19

Exert a direct antiviral activity against SARS-CoV20,21,22 — Quercetin’s general antiviral capacity has been attributed to three primary mechanisms of action:

Binding to the spike protein, thereby inhibiting its ability to infect host cells23

Inhibiting replication of already infected cells

Reducing infected cells’ resistance to treatment with antiviral medication

Inhibit the SARS-CoV-2 main protease.24

The Front Line Critical COVID-19 Care Alliance (FLCCC) early treatment protocol25 includes quercetin at a dose of 250 milligrams twice a day, in combination with 100 mg elemental zinc and 500 mg to 1,000 mg of vitamin C twice a day.