Viral Replication (Phase 1)

IN COVID-19 Protection

Living Document. Last Updated: 24th July, 2021

COVID-19 is complicated as is the various stages of treatments. I’m attempting to understand the phases and the various therapeutic targets. There should be TEAMS of health authorities doing this. I am a stickler for trying to understand things and getting answers to my questions, and it’s my duty as a human being to at least try and learn all I can about it so that we’re not completely clueless and dependant upon a broken health system who are sending people home to die (or without any treatment to prevent severe COVID). With that in mind, pay no attention to dosages I may of noted down along the way (you shouldn’t take medical dose information from a random person on the internet – except FLCCC which are all critical care doctors), and just use my notes to get a broad idea of where you’re at and what you can do if they send you home sick with “nothing” but a “call us if your lips to turn blue”.

There’s actually a lot we can do to prevent becoming one of the severe cases, and we can have a much better idea on what to do than the health authorities by dedicating some time to learning more about it.

Here is what COVID-19 looks like, and what to expect:

First, we have the Pre-Exposure phase – the ignored phase – the phase where we haven’t been exposed and the most optimal time to build a stronger front-line defence system. We can do things to increase our natural killer cells, and strengthen our mucosal / epithelial barrier, so that if we are exposed, our immune system can kick in a lot faster and stronger. The ‘main’ reason most children remain unaffected by COVID is because things in the younger immune system work more optimally than an adult against COVID. There are things we can do to help ‘turn those things back on’ during this period. Click Here to Support your Front-Line Defence

Next, we have “Phase 1” – after you’ve been exposed and have been sent home to self-quarantine for 14 days. This post is about Phase 1 – combatting the viral-replication phase to avoid proceeding to the other phases. 80% will only ever experience Phase 1.

Phases 2 & 3 would be when you are critically ill – only 20% will proceed to these phases, and this is when you will require medical treatment &/or hospitalization. If you have already progressed past the Viral Replication phase, my notes are not useful. When you’re at a more serious stage of the disease, the notes on this page, may actually ‘harm’ rather than ‘help’ because when the disease progresses to the inflammatory stage, that’s when you want to focus more on preventing inflammation and vascular complications (don’t delay if you are having severe symptoms – get help from your trusted health professional).

Phase 4 is the tail phase, aka Long COVID or Long-haulers. I haven’t researched this yet and only have a post for notes/videos.

The research I have focused on understanding is to help prevent us from ever reaching those more severe phases. Pre-Exposure Phase (build a stronger front-line defence) & Viral-Replication Phase (when you are sent home to self-isolate without medical treatment).

See: COVID-19 Phases & Targets – to learn more about symptoms of the various stages & for all resources/downloads.

This post is a living-document on Phase One – The Viral Replication Phase, which is what 80% of those exposed will experience. Many do not progress past this phase.

Phase One (Viral Replication)

(For 80% of people, this is the only phase)

  • Phase One: The “Viral Replication Period”. 2-14 days with an average of 5 days. This is when you get infected and the virus starts replicating. Here is the critical time to initiate early-stage protocols to inhibit viral replication and prevent severity. Symptoms include sore throat, nasal stuffiness, fatigue, headaches, body aches, loss of taste and/or smell, loss of appetite, nausea, diarrhoea, fever.

Therapeutic Targets in Phase 1: Viral Entry & Replication

  • Olfactory nerve carries the sense of smell to the brain (many report loss of smell/taste). (01) (02)

  • Heparan Sulfate ProteoGlycan (HSPG) is complex sugar that coats the outside of all human cells & holds the virus in place so that the next substance, furin, can do its job.

  • Furin coats all human cells. Its role in Covid-19 is to split the viral spike protein in two, so that one part fits tightly into its cellular receptor, ACE-2.

  • Angiotensin-converting enzyme 2 (ACE-2 Receptor) is the normal human protein found on the surface of many cells and is used as an entry point for SARS-CoV-2 infection.

  • CD147 was proposed as a possible alternative receptor for the SARS-CoV-2 spike protein. (03) (04) However, a study published in Nature in January 2021 found no evidence of it being an alternate entry receptor. (05) But then, 2 newer studies still referenced CD147 as a target, so either a cross-over in information due to delays in peer-reviewing during COVID or it may still be important. Ivermectin targets CD147, (06) and if more studies end up proving that CD147 is actually important, I will research to see if there are more therapeutics & update this post.

  • Transmembrane serine protease 2 (TMPRSS2) cuts a wedge out of both the Spike of the virus & the ACE-2 receptor on the cell, freeing the virus to fuse with the cell membrane. (07)

  • IMPα/β is responsible for transmitting viral proteins into the host cell nucleus and is a key component as to how the virus has been able to disable our cellular defence system. (08)

  • 3C-like proteinase (3CLpro) is the main protease (Mpro) used by SARS-CoV-2 to make viral proteins. It is responsible for processing the remaining nonstructural proteins of SARS coronaviruses, including RdRp and other subunits of the replicase–transcriptase complex (RTC). (09)

  • Papain-Like Protease (PLpro) is another protease to make viral proteins. (10)

  • RNA-dependent RNA polymerase or RNA replicase (RdRp) makes copies of the viral RNA in order to make new copies of the virus in infected cells.

  • Spike protein is a part of the virus that docks with ACE2 in order to infect cells.

  • Cytokines, including chemokines, interleukins, interferons and tumor necrosis factors (TNF), are small secreted proteins that mediate inflammation. Patients with severe COVID-19 requiring intensive care were found to have higher plasma levels of the proinflammatory cytokines GCSF, IP10, MCP1, MIP1A, and TNFα21. (11)
Viral Replication Targets
Download (as PDF)
Dietary sources of Vitamins
Download (as PDF)

Step 1: Reduce Viral Load:

Enters & Incubates in Upper Respiratory

Enters & Incubates in Upper Respiratory

Enters the Nose (Primarily): The principle site of entry of SARS-CoV-2 is the lining of the nose. Here the virus replicates, increasing in number before aspiration into the lungs, where pneumonia can occur.

Mucus-producing goblet cells and ciliated cells in the nose had the highest levels of both ACE2 and TMPRSS2 genes (of all cells in the airways). This makes these cells the most likely initial infection route for the virus.

Having multiplied in the nose, SARS-CoV-2 is in a strong position to invade both the brain and the blood vessels. The initial viral load in the nose is a key factor for determining the severity of infection.

The incubation period from exposure to illness is 2 to 14 days, with an average of 5 days. Unlike the flu, Covid-19 often starts gradually and the presenting symptoms are extremely variable. There may be no fever, even with severe illness. The level of viral RNA copies rises from undetectable to millions in the 1-3 days before development of symptoms and then decreases after the time of symptom onset.

Common early symptoms include fatigue, aches and pains, headache, sore throat, dry cough, stuffed or runny nose, nausea and loss of appetite. For some people, the first symptom is abdominal pain without respiratory complaints. (12)

Loss of smell and taste

Loss of smell and taste:

Supplements: Alpha-lipoic acid, Zinc/Quercetin Aspirin/Ivermectin/L-Lysine

Loss of smell and taste occurs frequently with Covid-19, often without nasal congestion. A European study found loss of smell in 86% of people with mild illness. When not associated with a stuffed nose, loss of smell is caused by swelling of an area at the top of the nose (olfactory cleft). Swelling is associated with viral invasion of a group of cells that surround and support the olfactory nerve, which carries the sense of smell to the brain called sustentacular cells. (13) (14) (15)

Swelling in this area can damage the olfactory nerve in 2 ways:
1.) There may be inflammatory chemicals (cytokines) released by the sustentacular cells that spill over and damage the nerve.
2.) Local swelling may put pressure on the nerve, creating what is called a pressure neuropathy. It usually clears within days to weeks.

Pressure neuropathies can be helped by the antioxidant alpha-lipoic acid, 600 mg/day, possibly in combination with gamma-linolenic acid (GLA).

Alpha Lipoic Acid (ALA) Dietary Sources: Spinach, Broccoli, Tomatoes, Brussels Sprouts, Peas, Potatoes, Yams, Beets, Carrots

Gamma Linolenic Acid (GLA*) Dietary Sources: Spirulina, Hemp Seeds, Oats, Barley, Evening Primrose Oil, Borage Oil, Blackcurrant Oil

*GLA is an Omega-6 Fatty Acid of which many of us already have an imbalance of too much Omega-6 to Omega-3 ratio.

Another (more anecdotal/observational in nature) writer wrote that a number of people restored their loss of smell with various protocols from his personal herbal protocol, to the combination of Zinc/Quercetin, to a combination of Ivermectin/Aspirin & reducing arginine-rich foods, or a combination of Aspirin/Ivermectin/L-Lysine (16)

Reduce Viral Load in the Nose & Throat

Reduce Viral Load in the Nose & Throat:

Gargling, Sulforaphane, Vitamin C, Nebulize

Vitamin C: Constant “all day” consumption
Vitamin C Dietary Sources: Guava, Mangos, Citrus (Oranges/Limes/Lemons), Tomatoes, Raw Peas, Red & Green Capsicum, Hot Green Chilli Pepper, Strawberries, Papaya, Broccoli, Pineapple, Brussels Sprouts, Kiwifruit, Cantaloupe, Cauliflower, Grapefruit, Steamed Potato

Gargling 3x a day:

  • 0.5% Povidone iodine (studies determine most effective) (17) (18)
  • Essential oils: hyssop, lemon, oregano, peppermint, spearmint, or tea tree (1 drop only with warm water/listerine)
  • Pharmacy-grade mouthwash (19)
  • Heparin (drug)
  • or if you cannot access any of those, at least gargle often with Listerine or Salt water.

Sulforaphane may have both a prophylactic and curative benefit against SARS-CoV-2. It reduces viral load in the nose, increases NK cell production, and displays antiviral activity that impairs viral reproduction & potent inhibitor of inflammation. It can also decrease inflammation for smokers, and has a protective effect on the lungs and increases the bodies ability to detoxify – immediately. (20)
Sulforaphane Dietary sources: Broccoli Sprouts (10 to 100 times the amount of Sulforaphane than Broccoli), Raw Broccoli (or Steamed from 1 to 3 mins), Raw Kale, Cabbage, Cauliflower, Brussels sprouts. You can also buy freeze-dried broccoli sprouts from organic health-food stores.
Supplement: “Sulforaphane glucosinolate” (broccoli seed extract)

Nebulizing – Saline with CDS (21), Hydrogen Peroxide (22), Iodine (23), or Heparin (24)
(Be sure to research dosages & purity/brand/safety if you intend to do this, or get advice from your trusted health professional – only a couple of drops of these are to be mixed with a lot of saline – do not take too much!)

Diffuser with Essential Oils (eucalyptus, frankincense, peppermint, or tea tree)

‘Viral Entry’ Targets

Joe Blow Version: This is all stuff to do with how the virus enters our cells. By targetting these entry points, the virus will have a harder time entering the cell, so will have less time to make copies, giving our immune system a chance to respond more rapidly to the intrusion.

Molecules in our cells that enable SARS-CoV-2 to quickly and efficiently enter:

There are four human molecules that, working together, enable SARS-CoV-2 to quickly and efficiently enter your cells: Heparan, Furin, ACE-2, and TMPRSS2. (25) (26)

Treatments that target each of these already exist and may prevent or limit viral entry and the damage it creates. They have been largely ignored in the trillion dollar race to develop antiviral drugs and vaccines. (27)

Step 2: Block/Disrupt Cell Entry Points

Heparan

Heparan

Prescription only: Heparin nasal spray, Heparin IV (hospitalized patients)

Potential Natural Candidates:
Lactoferrin/Colostrum? for the antiviral aspects
Red & Brown Seaweed? for the anticoagulant and antithrombotic

Heparan: The viral spike protein of SARS-CoV-2 sticks to heparan (complex sugar that coats the outside of all human cells) on the cell membrane, through a powerful electrical attraction. Heparan holds the virus in place so that the next substance, furin, can do its job.

Heparan Sulfate is a heavily sulfated glycoprotein that is present on the surface of many of our cells. A part of it, has to ‘bind’ with the spike protein at the receptor binding domain, and that ‘binding’ will allow the receptor binding domain to ‘open up’ and connect to the ACE-2 enzyme. If this binding doesn’t happen, the spike protein finds it difficult to connect to the ACE-2 enzyme: 80-90% reduction in the viruses entry into the cell if Heparan sulfate was blocked (in vitro).

Researchers have discovered that SARS-CoV-2 can’t grab onto ACE2 without a carbohydrate called heparan sulfate, which is also found on lung cell surfaces and acts as a co-receptor for viral entry. (28)

Source: DrBeen Medical Lectures (YouTube) (29)

A derivative of heparan called heparin is a drug that binds to the viral spike protein and can act as a decoy, filling up all the viruses heparan binding sites. (30) (31) Once it does that, the virus ultimately disintegrates.

Researchers have proposed administering heparin through a nebulizer, inhaled into the lungs, to limit viral spread in people who are sick. (32) Heparin comes from pig intestine however and there is a shortage of heparin due to swine flu that wiped out a large number of pigs in China (the biggest supplier of Heparin). Although DrBeen mentions only an IV-version of Heparin in his video about it.

The only dietary potentials I’ve come across for targeting Heparan haven’t been used in trials yet, but look promising:

Lactoferrin: One ‘in vitro’ study on lactoferrin (33) found that the mechanism of action of lactoferrin (LF) has broad-spectrum antiviral activity against SARS-COV-2 (in cell culture) and bovine lactoferrin (BLF) was even more potent than human lactoferrin.

The antiviral mechanism of action of lactoferrin was found to be mediated through binding to HSPGs on the host cell surface, thereby preventing viral attachment to the host cells. Several recent studies suggest that HSPGs serve as an attachment factor for the initial tethering of SARS-CoV-2 spike protein to host cell membrane and facilitates the subsequent binding to the specific receptor ACE2 (34)

Lactoferrin binds to heparan sulfate proteoglycans (HSPGs) on the host cell surface, which reduces viral attachment and subsequent viral entry. (35)

Lactoferrin is found in highest amounts in colostrum.

Colostrum is something I’ve already researched previously for use against SARS-CoV-2 (and for Cancer), and has already been studied and showed to work well in inhibiting the attachment of viruses to cells in the body and the replication of viruses in cells and shown to improve immune function in general. (36) Since it already works in a broad way against viruses, we don’t need to wait for human trials for it to be beneficial (against viruses in general), and so it won’t hurt to add it to our COVID-19 Toolbox. (37) (38)

Possible action of (1) lactoferrin by occupying binding sites of (2) SARS-CoV-2 that causes COVID-19. (3) Entry into host cells occur when SARS-CoV-2 first attaches to Heparan sulfate proteoglycans (HSPGs). This attachment initiates the first contact between the cell and the virus, concentrating the virus on the cell surface, (4) followed attaching of the virus to the host receptor (ACE2) and association and entering are then facilitated via clathrin-coated pits (5) Virus replication can then happen inside the cell. (6) One of the characteristics of Lactoferrin, is that it attaches to HSPGs. (7) Currently we do not know if ACE2 is also a receptor for lactoferrin. (8) Lactoferrin may block the entry of SARS-CoV-2 into the host cell, by occupying HPSGs, thereby preventing SARS-CoV-2 initial attachment and accumulation on the host cell membrane. COVID-19 infection Source: The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria (39)

Heparin, the only ‘drug’ that seems to target Heparan, may have a dual action in regards to COVID-19: as an antiviral to decrease viral attachment (as already mentioned), but it also has anticoagulant activity (reducing the risk of blood clots and strokes). (40) So Colostrum might be our best supplement for the Heparan disruption, but we will need to add other things for the anticoagulant aspect:

Seaweed: Although there are already many anticoagulant and antithrombotic drugs such as aspirin, heparin, etc., scientists have found that seaweeds are rich in natural anticoagulant and antithrombotic substances, in particular, red and brown seaweeds contain many sulfated polysaccharides with medical functions similar to heparin. (41) The seaweed extracts appear to work against SARS-CoV-2 via what’s known as a decoy technique (the virus could just as easily be persuaded to lock onto a decoy molecule that offers a similar fit). (42) By binding tightly to the spike protein of SARS-CoV-2, seaweed’s sulfated polysaccharides may act as decoys to interfere with the spike protein binding to the heparan sulfate co-receptor, which could effectively deter viral infection. (43) In an early (1999) study, 16 extracts of British Columbian seaweeds were investigated and 15 of them were found to have direct virus-killing abilities. (44) (45)

Furin

Furin

Supplements: Luteolin, Folic Acid (Vitamin B9), Bromelain, Vitamin B12, Melanin & Vitamin D
Additionally: Vitamin C, Vitamin D, Vitamin K, Zinc
Vitamin B12 sublingually ( “under the tongue”) at doses 500mcg+, minimum 3 times per week.

Furin also coats all human cells. Its role in Covid-19 is to split the viral spike protein in two, so that one part fits tightly into its cellular receptor, ACE-2. Without priming by furin, the viral spike protein forms a very weak attachment to the cellular receptor and the entry of virus into cells becomes slow and inefficient. 

The place on the viral spike protein that sticks to heparan (the heparan binding site) overlaps the place where it’s split by furin (the furin cleavage site). This relationship has enabled the pandemic, because it dramatically enhances the speed with which the virus enters human cells. (46)

Furin is a protein implicated in viral diseases, which cleaves some glycoproteins from the viral envelope and increases the viral fusion to host cell membranes.

Zinc is super important for immune cells and prevents some pathogens from being able to latch on to your tissue in your respiratory system, as well as being a Furin Inhibitor in combination with copper. (47) Zinc was shown to inhibit furin (proprotein convertase) which is important in the pathogenesis of many viruses. (48)
Zinc Dietary Sources: Legumes: Chickpeas, Lentils, Beans (sprouted increases absorption), Nuts & Seeds: Hemp seeds, Squash & Pumpkin seeds, Sesame seeds, Pine Nuts, Cashews, Sunflower seeds, Pecans, Chia seeds, Flaxseeds, Brazil Nuts, Almonds.
Given that we need to have a lower arginine consumption during the viral replication phase, it’s probably wiser in this phase to take a zinc supplement rather than rely on dietary sources (especially avoiding nuts which are high arginine food sources).
Zinc Supplement: zinc gluconate, zinc picolinate, or zinc acetate – (NOT zinc oxide*).
*zinc oxide is known to be less bioavailable (don’t forget you can get zinc from your diet making it even more bioavailable).

Help Zinc get into your cells:

  • Quercetin with Vitamin C (to boost Quercetin absorption)
  • Selenium (Zinc needs selenium to function properly)
  • Niacin (Vit B3) (Zinc works synergistically with Niacin)
  • Green Tea (ECGC)

Folic Acid / Folate / Vitamin B9: Recently, it was noted that folic acid (folate / vitamin B9) was able to inhibit furin, preventing binding by the SARS-CoV-2 spike protein, preventing cell entry and virus turnover. (49) B9 can inactivate the furin endoprotease that is crucial for the SARS-CoV-2 virus to enter its host cell. (50)
Folic Acid/Folate/Vitamin B9 Dietary Sources: Red Leaf Lettuce, Edamame, Savoy Cabbage, Artichokes, Kimchi, Chives, Broccoli Raab, Arugula/Rocket, Collards, Kelp Seaweed, Parsley, Chinese Broccoli, Chicory Greens, Okra, Chinese Cabbage, Chicken Liver, Pak-Choi, Butterhead Lettuce, Turnip Greens, Asparagus, Cos or Romaine Lettuce, Endive, Raw Spinach (51)

Vitamin B12 is an efficient nutraceutical for almost all of the nCOV-2 drug targets including the host protease furin. (52)
Vitamin B12 Dietary Sources: Trout, Salmon, Canned tuna, Milk, Chocolate, Beef, Greek yogurt, Swiss cheese, Ham, Egg, Chicken.

Update July 17, 2021:
Vitamin B12 sublingually ( “under the tongue”) at doses 500mcg+, minimum 3 times per week.

After reading a 78 page document put forward by one of the doctors treating COVID-19 in a group I’m in (from Barcelona), I am now adding this for anyone residing in a country that has chlorinated water. He considers this an urgent message for the population & governments. (If he’s right, then the malabsorption of b12 in some populations are predisposing us to worsened outcomes & it will even help those with long-covid). He goes into detail of the studies in the document but specifically mentions that if you have any liver, kidney, other severe diseases or under 8 years old, to seek advice from your doctor about dosages). (53)

Luteolin is a dietary molecule that is a furin inhibitor and has the capacity to block the entry of SARS-CoV into host cells. Not only can it interrupt the furin binding, its also an antioxidant, a free radical scavenger, an inflammatory agent and an immune system modulator as well as being active against several cancers. (54) (55)
Luteolin Dietary Sources: Oregano, Bird Chilli, Parsley, Onion Leaves (Spring Onion), Celery Seeds, Thyme, Green peppers, Chamomile, Juniper Berries.

Bromelain also inhibits SARS‐CoV‐2 infection via targeting ACE‐2, TMPRSS2, and the Spike protein.
Bromelain Dietary Sources: Pineapple Juice (with Stem)

Melanin & Vitamin D: Synergy of melanin and vitamin-D may play a fundamental role in preventing SARS-CoV-2 infections and halt COVID-19 by inactivating furin protease. (56)

Other possible vitamin/mineral Furin interactions: Vitamin C, Vitamin K.

ACE-2 Receptor

ACE-2 Receptor

Supplements: Quercetin, Bromelain, NAC, Luteolin

Potential Supplement Candidates:
Curcumin – awaiting trial outcome
Nigella Sativa – in theory
Folic Acid – in silico

Prescription Drugs: Ivermectin, Hydroxychloroquine, or Umifenovir

Virion infection of host cells is initiated by the viral spike (S) protein binding to ACE2. Infection of epithelial cells begins when the spike glycoprotein trimer (S) of the virus binds to the Angiotensin-converting enzyme 2 (ACE2). The viruses receptor-binding domain (RBD) binds with a very strong affinity to ACE-2.

ACE2 is present in the nasal passages, airways and alveoli, and expressed by the epithelial cells covering organs like the lungs, intestines and blood vessels. The ACE2-expressing cells in oral tissues, especially in epithelial cells of tongue, might provide possible routes of entry.

ACE-2 is a protein embedded in the human cell membrane, and the centrepiece for viral entry, so it’s called the cellular receptor. It attaches to the receptor binding domain of the viral spike protein.  Unlike furin or heparan, ACE-2 is only found in certain types of cells, where it bridges the entire thickness of the membrane, from outside to inside.  SARS-CoV-2 is most likely to infect cells that express ACE-2 in their membranes.

ACE-2 is an enzyme that is vitally important for your health. It protects your blood vessels, your heart, your brain, your lungs, your kidneys and your bone marrow from many types of damage, inhibits inflammation, prevents abnormal blood clotting and enables healing without scarring. When a corona virus uses ACE-2 to enter cells, the protein loses its enzyme activity. 

Loss of ACE-2 underlies all the terrible complications of Covid-19, including pneumonia, heart failure, blood clots, kidney failure, strokes, seizures, brain fog, purple toes, loss of lymphocytes, excessive inflammation and autoimmune disease.

Comparative analysis showed that ACE2 expression in kidney cells was no less than that in the lung, esophagus, small intestine, and colon, suggesting that the kidney may be an important target organ for SARS-CoV-2. According to the public data analysis, the level of ACE2 expression in adipose tissue (body fat) was higher than that in lung tissue, which was indicative of the possibility that adipose tissue was also a potential target of SARS-CoV-2. The SARS-CoV-2 S protein has 10 to 20 times more affinity to bind to ACE-2 compared to SARS-CoV.

Some scientists are attempting to develop drugs that prevent the viral spike protein from attaching to ACE-2. There is a natural product that does just that: quercetin, a bioflavonoid found in onions, apples and other fruits and vegetables. Quercetin is able to insert itself between ACE-2 and the receptor binding domain of the viral spike protein. It’s like a friendly bystander breaking up a fight. (57)
Quercetin Dietary Sources: Green Tea, Capers, Red Onion, Shallots, Red Apples (Unskinned), Grapes, Berries, Cherries, Scallions, Kale, Cherry Tomatoes (Organic = up to 79% more), Broccoli, Brussels Sprouts, Cabbage, Green & Yellow Bell Peppers, Almonds, Pistachios, Cooked Asparagus, Elderberry Tea

Joe Blow Version: Drugs, Supplements, or Food that can delay (Hinder/Block/Obstruct/Interfere with) the Virus entering the cell (where it does it’s replicating). Disrupting this process gives the body more time to gather an army. Like standing in between a fight to bide time for backup to arrive.

Quercetin protects the ACE-2 receptor, (58) has the capacity to block the entry of SARS-CoV into host cells, (59) (60) and it also works with zinc to prevent RNA replication. (61)
Quercetin Dietary Sources: Green Tea, Capers, Red Onion, Shallots, Red Apples (Unskinned), Grapes, Berries, Cherries, Scallions, Kale, Cherry Tomatoes (Organic = up to 79% more), Broccoli, Brussels Sprouts, Cabbage, Green & Yellow Bell Peppers, Almonds, Pistachios, Cooked Asparagus, Elderberry Tea

  • Increase Quercetin Absorption: (Vitamin C or Bromelain)
  • Vitamin C helps with Quercetin absorption which helps protect the ACE-2 receptor. There is evidence that vitamin C and quercetin co-administration exerts a synergistic antiviral action due to overlapping antiviral and immunomodulatory properties and the capacity of ascorbate to recycle quercetin, increasing its efficacy.
  • Bromelain Dietary Sources: Pineapple Juice (with Stem)
  • The FLCCC guide mentions that a mixed flavanoid supplement containing quercetin, green tea catechins and anthrocyanins (from berries) may be preferable to a quercetin supplement alone (62)

Ivermectin docks between the spike protein and the ACE-2 receptor of our cells, making a barrier that hinders it’s ability to connect to the ACE-2 receptor (making it harder for it to infect that cell). (63) (64) (65)
Learn all the ways Ivermectin combats COVID-19

Umifenovir is a new antiviral agent that targets S protein/ACE-2 interaction and it has a mechanism of action that inhibits the viral envelope’s membrane fusion. (66)

Hydroxychloroquine Through inhibition of the ACE2 glycosylation, Hydroxychloroquine can block SARS-CoV-2 entry to the cell. (67)

May also help disrupt Spike to ACE-2 binding:

  • Curcumin-Piperline may ‘hypothetically’ be used to block the viral spike protein from the ACE2 receptor. (68) Awaiting the outcome of a trial in Iran. (69)
    Curcumin Dietary Sources: Turmeric, Curry Powder, Mango Ginger, with Piperline (Black Pepper)
  • Bromelain inhibits SARS‐CoV‐2 infection via targeting ACE‐2, TMPRSS2, and spike protein. (70) (71)
    Bromelain Dietary Sources: Pineapple Juice (with Stem)
  • NAC may impair ACE2 actions when coupled with SARS-Cov-2. (72)
  • Nigella Sativa: Black seed might block the entry of the virus into pneumocytes (block the SARS-CoV-2 entry via ACE2) (73)
  • Luteolin displayed binding affinity with ACE2. (74)
    Luteolin Dietary Sources: Oregano, Bird Chilli, Parsley, Onion Leaves (Spring Onion), Celery Seeds, Thyme, Green peppers, Chamomile, Juniper Berries.
  • Folic acid and its derivatives can prevent the interaction of S protein with ACE-2 receptor (in silico). (75)
    Folic Acid/Folate/Vitamin B9 Dietary Sources: Red Leaf Lettuce, Edamame, Savoy Cabbage, Artichokes, Kimchi, Chives, Broccoli Raab, Arugula/Rocket, Collards, Kelp Seaweed, Parsley, Chinese Broccoli, Chicory Greens, Okra, Chinese Cabbage, Chicken Liver, Pak-Choi, Butterhead Lettuce, Turnip Greens, Asparagus, Cos or Romaine Lettuce, Endive, Raw Spinach (76)

TMPRSS2

TMPRSS2

Prescription: Ivermectin
Over-the-Counter: Bromhexine
Supplements/Dietary: Bromelain (Pineapple Juice with Stem)
Chinese Herbs: Baicalein (from the Chinese herb, Scutellaria baicalensis)

Transmembrane serine protease 2 (TMPRSS2) (“tempress-2”), like ACE-2, is an enzyme in human cell membranes. Like ACE-2, it is only found in certain types of cells. As the viral spike protein locks into ACE-2, TMPRSS2 cuts a wedge out of both, destroying the beneficial activity of ACE-2 and freeing the virus to fuse with the cell membrane. The cells that the virus can enter most quickly and efficiently are those few cell types that express both ACE-2 and TMPRSS2 in their membranes.

The highest co-concentration of these two enzymes demonstrated so far occurs in cells that line the nose. Co-expression is also found in the lungs, the salivary glands, the lining of the heart and blood vessels, testicles and the small and large intestines.

In these cells, it appears that the rate-limiting step for viral entry is the level of TMPRSS2, not the level of ACE-2, because TMPRSS2 speeds the rate of cell entry about one hundred fold. Depending on the type of cell, inhibition of TMPRSS2 can reduces viral entry by over 90%.  (77)

Cleavage or priming of the S protein by TMPRSS2 is essential for the fusion of the virus with the ACE2 receptor needed for viral entry and spread of SARS-CoV-2. (78) Hoffmann et al. confirmed that SARS-CoV-2 enters the host cells mainly via binding and fusion with ACE2. Inhibition of TMPRSS2 activity is thus an excellent target for antiviral intervention. (79)

Ivermectin
Ivermectin was found to strongly and stably bind with TMPRSS2 which indicates that Ivermectin has the potential to disrupt host-virus interaction. It was even found to be more effective than Remdesivir and lower than HCQ – suggesting the use of either IVM and/or HCQ could be utilized for this function. (80) (81) Learn all the ways Ivermectin combats COVID-19.

Bromhexine
Bromhexine (cough medicine for both prophylactic and treatment). (82)
Bromhexine, which has been used in Europe, Asia and Latin America for decades. A randomized clinical trial in Iran found that addition of bromhexine to usual care at the time of hospitalization produced an 80% reduction in ICU admissions and the need for mechanical ventilation and reduced the death rate from 12% to zero. (83)
Lucas et al. showed a decrease in the frequency of metastases and a slowdown of the spread of metastases in mice with prostate cancer using TMPRSS2 inhibitors. In particular, they identified bromhexine, an FDA-approved ingredient in mucolytic cough suppressants, as a potential TMPRSS2 inhibitor for their application. Bromhexine is orally readily bioavailable. Bromhexine is an over-the-counter (OTC) drug (84) that is affordable with proven safety. (85) Typically bromide compounds, especially aromatic bromide compounds, show a relatively high binding affinity for serine-containing peptide sequences, proteins, and enzymes. Lucas et al. show that this effect is due to a selective inhibition of TMPRSS2 by bromhexine. (86)
Clinical trials have been registered to explore the therapeutic potential of oral bromhexine hydrochloride in patients with COVID-19. (87) In one pilot study, they reported that the results indicated that Bromhexine might improve lung ventilation and may have a protective effect against COVID-19-induced acute lung injury due to it’s ability to inhibit TMPRSS2. (88) Another study concluded that Bromhexine is not an effective treatment for hospitalized patients with COVID-19. (89) A small study focused on it’s prophylaxis potential for Medical Personnel and concluded that Bromhexine as a prophylaxis was associated with a reduced rate of symptomatic COVID-19. (90) Bromhexine is an effective drug in the management and treatment of Covid-19 pneumonia via targeting ACE2/ TMPRSS2 pathway. However, prospective and controlled clinical trials are recommended to confirm this observation. (91) This site keeps up-to-date with the current trials on Bromhexine & COVID-19. (92)

Bromelain
Bromelain inhibits SARS‐CoV‐2 infection via targeting ACE‐2, TMPRSS2, and spike protein. (93) (94)
Bromelain Dietary Sources: Pineapple Juice (with Stem)

Chinese herbs: Baicalein
Baicalein (from the Chinese herb, Scutellaria baicalensis) (95)

Remdesivir
Remdesivir is a prescription drug that has been reported as potentially being useful for this purpose. (96) However, it is way over-priced (over USD $3k for a 5 day treatment) (97) and in this case study 4 out of 5 patients had to stop using it due to side effects. (98) I am not going to be someone that suggests something that is not only ripping people off (production cost for remdesivir is estimated at US$0.93 per day of treatment but they charge over $500 a day?), (99) but may be potentially pretty useless (100) (101) (102) or potentially dangerous, when there are safer and cheaper alternatives, with less adverse side effects.

It also seems that there may be a bit of bias that it was even approved in the first place: NIH brought together a panel of experts to make treatment recommendations, (103) eight of whom had accepted research support or consulting fees from Gilead, the manufacturer of remdesivir. (104) I don’t like seeing this kind of thing, over and over again throughout this entire pandemic.

Ivermectin costs less than $10, can be made by any compounding pharmacy, works better than the drugs that cost $3k, yet this cheaper, safer and more effective choice gets suppressed. That smells funky to me. “People Over Profits” should be the only goal whether there’s a pandemic or not.

Potential Prescription Drugs:

Combination of hydroxychloroquine and a clinically-tested TMPRSS2 inhibitor, (105) lopinavir and valrubicin (have been proposed for more research for dual inhibition of TMPRSS2 & ACE2) (106), and an experimental Anti Viral drug called N-0385 (most potent inhibitor of TMPRSS2 reported to date). (107) (108)

‘Viral Replication’ Targets

Assuming we haven’t effectively stopped the virus from ‘entering’ the cells using the above methods, the next thing we can target is it’s replication process.

Once the virus has gained entry to the cell, the virus has the ability to turn off the cell’s defence system, it then releases it’s RNA (instructions to create new copies) into the cell and uses its own RNA copying machine (called a polymerase) to make duplicates of RNA inside the vesicles. Some of the copies are utilized to make more viral proteins (such as the spike), and others are packaged into new virus particles (which break out of the cell).

Step 3: Disrupt the Replication process:

'Viral Replication' Targets

Prescription: Ivermectin, Fluvoxamine
Over-the-Counter: Bromhexine
Supplements/Dietary: L-Lysine, Arginine-Depletion, Sulforaphane, Luteolin, Selenium, Vitamin B9, Vitamin C, NAC, Zinc/Quercetin

L-Lysine
L-lysine blocks arginine, an amino acid the virus needs in order to replicate. It also helps the body absorb calcium, iron, and zinc. Several viruses have been proven to be stopped indirectly by the dietary essential amino acid, L-Lysine. This is because at least some viruses depend on the amino acid L-arginine to replicate, and L-Lysine has a chemical structure so similar to L-arginine that at least some viruses mistakenly incorporate L-Lysine instead of the L-Arginine they need. As a result, the virus lacks sufficient L-Arginine to replicate. It’s a competitive effect. Changing the diet to favour a high ratio of L-Lysine to L-Arginine directly affects the replication of these viruses. (109)
High in Lysine, Low in Arginine Foods: Apples, Apricots, Asparagus, Avocados, Bananas, Beets, Beans, Bok Choy, Cantaloupe, Capsicum, Carrots, Cauliflower, Celery, Cherries, Corn, Ginger, Guava, Kale, Leeks, Lentils, Lettuce (red leaf), Mango, Melon, Nectarines, Okra, Peaches, Pears, Pineapple, Plums, Potatoes, Squash, Spinach, Strawberries, Sweet Potato, Tomato, Turnip Greens, Watercress, Zucchini (110)

Arginine-Depletion
A group of physicians in New York have gone on record to advocate arginine-depletion as a therapeutic approach to COVID-19 coronavirus infection, though they advocate use of an arginine-depleting enzyme rather than supplemental lysine. (111)

Cease consumption of High Arginine Food Sources especially Caffeine: Arginine appears to be a key metabolite important for successful viral replication. Arginine residues were found on the spike (S) protein and there are clear steps in the SARS-CoV-2 lifecycle that rely on conserved arginine residues. (112) Arginine is also a key substrate in the host inflammatory response, and reduction of serum plasma arginine levels could plausibly attenuate the severe inflammatory response in SARS-CoV-2 infection. (113) (114) Caffeine increases arginine availability. (115) And another study says that the arginine motif at the S1/S2 site of the S protein has been shown to be a critical cleavage site for host machinery after viral binding. Results indicate that the presence of several arginine residues at the S1/S2 site is required for efficient SARS-2-S proteolytic processing in human cells and also confers high cleavability to SARS-S. (116)

Diet (Eliminate): Eliminate Caffeine Immediately. Reduce or Eliminate High Arginine Food Sources (Peanuts, Walnuts, Hazelnuts, Pumpkin seeds, Chocolate, Spirulina, Squash, Oats, Wheat, and Supplements or Vitamins you might be taking that include Arginine (like those found in muscle-building protein shakes), etc.

Sulforaphane
Sulforaphane displays antiviral activity that impairs viral reproduction. Sulforaphane may have both a prophylactic and curative benefit against SARS-CoV-2. It reduces viral load in the nose, increases NK cell production, and displays antiviral activity that impairs viral reproduction & potent inhibitor of inflammation. It can also decrease inflammation for smokers, and has a protective effect on the lungs and increases the bodies ability to detoxify – immediately. (117)

Luteolin
Luteolin displays antiviral activity by inhibiting RNA replication and viral reactivation (118)
Luteolin Dietary Sources: Oregano, Bird Chilli, Parsley, Onion Leaves (Spring Onion), Celery Seeds, Thyme, Green peppers, Chamomile, Juniper Berries.

Selenium
Selenium is a trace element: potent nutritional antioxidant, anti-inflammatory, and anti-clotting.
Diet (Add): Brazil Nut (1 per day) for Selenium* (*because deficiency increases replication). Selenium-deficiency influences several aspects of RNA viruses such as mutations, replication and virulence. (119)
Selenium Dietary Sources: Brazil Nuts, Salmon, Tuna, Sardines, Halibut Turkey, Chicken, Eggs, Cottage Cheese, Mushrooms, Navy beans, Sunflower seeds, Grass-fed beef, Beef Liver, Oats

Vitamin B9
Vitamin B9 proved one of the best inhibitors for all viral targets. with best binding with Furin, Spike, RdRP, NSP3 proteins. (120)
Folic Acid/Folate/Vitamin B9 Dietary Sources: Red Leaf Lettuce, Edamame, Savoy Cabbage, Artichokes, Kimchi, Chives, Broccoli Raab, Arugula/Rocket, Collards, Kelp Seaweed, Parsley, Chinese Broccoli, Chicory Greens, Okra, Chinese Cabbage, Chicken Liver, Pak-Choi, Butterhead Lettuce, Turnip Greens, Asparagus, Cos or Romaine Lettuce, Endive, Raw Spinach (121)

Vitamin C
Vitamin C in vitro and in vivo clinical trials showed significant reduction of viral replication without any insight to proper inhibitory mechanisms. (122)
Vitamin C Dietary Sources: Guava, Mangos, Citrus (Oranges/Limes/Lemons), Tomatoes, Raw Peas, Red & Green Capsicum, Hot Green Chilli Pepper, Strawberries, Papaya, Broccoli, Pineapple, Brussels Sprouts, Kiwifruit, Cantaloupe, Cauliflower, Grapefruit, Steamed Potato

NAC
NAC is powerful at overcoming toxicity, breaks mucus apart, reduces viral replication, and produces glutathione.

Prescription Drugs:

Ivermectin (0.2-.0.4mg /kg per dose with meals – one dose daily for 5 days or until recovered.
Fluvoxamine 50mg twice daily for 10-14 days if minimal response after 2 days of ivermectin (or in regions with more aggressive variants).
Check FLCCC for dosage guidelines for updated recommendations. Check drugs.com for potential medicine interactions.

We can get really specific with our treatments by disrupting the viral replication processes that are known SARS-CoV-2 targets:

  • IMPα/β is responsible for transmitting viral proteins into the host cell nucleus and is a key component as to how the virus has been able to disable our cellular defence system. (123)
  • 3C-like proteinase (3CLpro) is the main protease (Mpro) used by SARS-CoV-2 to make viral proteins. It is responsible for processing the remaining nonstructural proteins of SARS coronaviruses, including RdRp and other subunits of the replicase–transcriptase complex (RTC). (124)
  • Papain-Like Protease (PLpro) is another protease to make viral proteins. (125)
  • RNA-dependent RNA polymerase or RNA replicase (RdRp) makes copies of the viral RNA in order to make new copies of the virus in infected cells.
  • Spike protein is a part of the virus that docks with ACE2 in order to infect cells.
  • Cytokines, including chemokines, interleukins, interferons and tumor necrosis factors (TNF), are small secreted proteins that mediate inflammation. Patients with severe COVID-19 requiring intensive care were found to have higher plasma levels of the proinflammatory cytokines GCSF, IP10, MCP1, MIP1A, and TNFα21. (126)

IMPα/β

IMPα/β

Prescription Drugs: Ivermectin

Ivermectin disrupts the importin (IMP) α/β receptor which is responsible for transmitting viral proteins into the host cell nucleus. (127) (128) (129) (130) (131) (132) (133) (134)

Normally when a cell is under stress, it produces enzymes to protect itself which also signals the neighbouring cells that it’s under attack which gets them primed and ready to defend themselves. SARS-CoV-2 has the ability to turn that signal off.

When a cell is stressed, it secretes interferon and tumor necrosis factor. These chemical substances helps protect the cell itself, and the neighbouring cells detect this substance, which enables them to get ready.

SARS-CoV-2 blocks our cell from secreting these enzymes by sending a message to the brain of the cell – the nucleus (via our proteins importin (IMP) α/β telling it not to defend itself (not to make those interferon and tumor necrosis factor).

Ivermectin takes away SARS-CoV-2’s super-power. The reason this virus is so damaging and able to replicate so fast, is because our cells defence system has been shut-down.

Ivermectin disrupts these messages resulting in better cellular defence by our tissues. How does Ivermectin do that?

Ivermectin blocks the binding of the virus message with importin (IMP) α/β because when Ivermectin is in the cells, it’s already ‘occupying’ those importins. (135) (136)

The result being that the virus can not use importin (IMP) α/β to communicate to the brain of the cell to tell it not send out those enzymes.

Now the nucleus will sense the stress, create the enzymes, warn the neighbouring cells and those enzymes also help protect the cell itself. Learn all the ways Ivermectin combats COVID-19. (137) (138)

I have not found any other treatments, dietary or otherwise, that can do what Ivermectin does to disrupt this particular function of the virus – although I’m certain others exist and will continue to research.

RdRp

RdRp

Supplements: Zinc, Zinc Ionophore, Quercetin, Luteolin, and Vitamin B9
Drugs: Ivermectin, Doxycycline, Famotidine, Favipiravir, HCQ, Lymecycline, Remdesivir

Zinc
Zinc will slow down the replication through inhibition of enzyme RNA polymerase (COVID-19 is an RNA virus and requires the RNA polymerase to replicate). (139) Zinc directly inhibited the coronaviral RNA-dependent RNA polymerase, which functions as the core enzyme of the RNA viral synthesizing machinery. (140).

Zinc Ionophore (Help Zinc get into your cells)
Our cells won’t allow much zinc in, so a zinc ionophore is needed to help zinc’s entry into the cells, and once it’s in the cells, its able to block the enzyme RNA-dependent RNA polymerase (turn off viral replication). (141)

So we need to take a zinc ionophore to help more zinc enter the cells. The easiest zinc ionophore to access is Quercetin (a bioflavonoid found in onions, apples and other fruits and vegetables, etc.) which is available also as a supplement. There are already standard protocols available for using Quercetin in combination with Zinc as both prevention and treatment. Check FLCCC for dosage guidelines as they are keeping up-to-date with the latest research.

  • Quercetin with Vitamin C (to boost Quercetin absorption) (142)
    Quercetin Dietary Sources: Green Tea, Capers, Red Onion, Shallots, Red Apples (Unskinned), Grapes, Berries, Cherries, Scallions, Kale, Cherry Tomatoes (Organic = up to 79% more), Broccoli, Brussels Sprouts, Cabbage, Green & Yellow Bell Peppers, Almonds, Pistachios, Cooked Asparagus, Elderberry Tea
  • Selenium (Zinc needs selenium to function properly)
    Selenium Dietary Sources: Brazil Nuts, Salmon, Tuna, Sardines, Halibut Turkey, Chicken, Eggs, Cottage Cheese, Mushrooms, Navy beans, Sunflower seeds, Grass-fed beef, Beef Liver, Oats
  • Niacin (Vit B3) (Zinc works synergistically with Niacin)
    Niacin (Vitamin B3) Dietary Sources: Nutritional Yeast, Liver, Anchovies, Chicken Breast, Maitake Mushrooms, Green Peas, Tuna, Beef Kidney, Portabella Mushrooms, Swordfish, Pork Chops, Salmon, Broccoli Raab, Sirloin Steak, Lamb, Mackerel, Turkey, Avocado, Peanuts, Potatoes
  • Green Tea (ECGC) (143)

Ivermectin disrupts the RdRp enzyme of the virus reducing the virus’s replication (RdRp’s function is to create more Messenger RNA viruses). (144) (145) (146) (147) (148) (149)
Learn all the ways Ivermectin combats COVID-19.

Luteolin
Luteolin displays antiviral activity by inhibiting RNA replication and viral reactivation. (150)
Luteolin Dietary Sources: Oregano, Bird Chilli, Parsley, Onion Leaves (Spring Onion), Celery Seeds, Thyme, Green peppers, Chamomile, Juniper Berries.

Vitamin B9
Vitamin B9 proved one of the best inhibitor for all viral targets. with best binding with Furin, Spike, RdRP, NSP3 proteins. (151)
Folic Acid/Folate/Vitamin B9 Dietary Sources: Red Leaf Lettuce, Edamame, Savoy Cabbage, Artichokes, Kimchi, Chives, Broccoli Raab, Arugula/Rocket, Collards, Kelp Seaweed, Parsley, Chinese Broccoli, Chicory Greens, Okra, Chinese Cabbage, Chicken Liver, Pak-Choi, Butterhead Lettuce, Turnip Greens, Asparagus, Cos or Romaine Lettuce, Endive, Raw Spinach (152)

Drugs: Doxycycline, Famotidine, Favipiravir, HCQ, Ivermectin (Ivm), Lymecycline, Remdesivir

3CLpro/Mpro

3CLpro/Mpro

Supplements: Vitamin B9, ECGC, Luteolin
Chinese Herbs: Glycyrrhizin
Drugs: Ivermectin

The viral main proteinase (Mpro, also called 3CLpro) controls the activities of the coronavirus replication complex, and is an attractive target for therapy. (153)

Ivermectin blocks more than 85% of 3CLpro activity of SARS-CoV-2. IVM disrupts the viral main proteinase, resulting in the reduction in virus replication. (154) (155)
Learn all the ways Ivermectin combats COVID-19.

Vitamin B9 inactivates protease 3CLpro, which is vital in the replication of all coronaviruses (156)
Folic Acid/Folate/Vitamin B9 Dietary Sources: Red Leaf Lettuce, Edamame, Savoy Cabbage, Artichokes, Kimchi, Chives, Broccoli Raab, Arugula/Rocket, Collards, Kelp Seaweed, Parsley, Chinese Broccoli, Chicory Greens, Okra, Chinese Cabbage, Chicken Liver, Pak-Choi, Butterhead Lettuce, Turnip Greens, Asparagus, Cos or Romaine Lettuce, Endive, Raw Spinach (157)

ECGC (Green Tea) – green tea, muscadine grape, cacao, and dark chocolate also inhibited the Mpro activity. (158)

Luteolin C3/luteolin and C43/abyssinone II were disclosed as potent inhibitors with enhanced binding affinity compared to remdesivir against Mpro/3CLpro, PLpro and ACE2 of COVID-19. (159)
Luteolin Dietary Sources: Oregano, Bird Chilli, Parsley, Onion Leaves (Spring Onion), Celery Seeds, Thyme, Green peppers, Chamomile, Juniper Berries.

Glycyrrhizin, the most active component of Chinese licorice, blocks SARS-CoV-2 replication mainly by inhibiting the main protease Mpro. (160)

Potential Candidates:

Hypericin and cyanidin-3-O-glucoside inhibit M pro in vitro. (161)

  • Hypericin (St. John’s Wort)
  • Cyanidin 3-O-Glucoside (Black Grapes, Cranberries, Elderberry, Blackberries, Blackcurrant, Gooseberry, Blueberry, Raspberry, Redcurrant, Strawberry, Nectarines, Peaches, Plums, Cherries, Orange Juice, Pomegranate juice, Black beans, Olives, Red Lettuce (162)

Curcumin – Curcumin was not tested as part of this drug repurposing study; nonetheless, docking results predict a plausible role as an Mpro inhibitor (163). Khaerunnisa et al. examined the role of several phytochemical compounds such as curcumin that may have the potential to inhibit the COVID-19 infection by molecular docking. Curcumin showed relatively low binding energies and inhibition constants. They suggested that curcumin could have a potential inhibitory effect on COVID-19 Mpro and could potentially act as a therapeutic agent (Khaerunnisa, Kurniawan, Awaluddin, Suhartati, & Soetjipto, 2020). (164)
Curcumin Dietary Sources: Turmeric, Curry Powder, Mango Ginger, with Piperline (Black Pepper)

Magnesium Ascorbate, a buffered (non-acidic) form of Vitamin C (Ascorbic acid), was found to be the top lead compound among 106 nutraceuticals against Mpro (in silico). (165)

Ebselen is a synthetic organoselenium drug molecule with anti-inflammatory, anti-oxidant and cytoprotective activity. (166)

Antibacterial drugs like lymecycline, demeclocycline, doxycycline have shown to bind effectively to the binding site of 3-CL pro in computational studies conducted by Canrong Wu et al. (167)

Papain-Like Protease (PLpro)

Papain-Like Protease (PLpro)

Zinc + Zinc Ionophore: Zinc + Quercetin, Zinc + Green Tea, Zinc + HCQ,
Improve Zinc function: Quercetin, Vitamin C, Selenium, Niacin (Vitamin B3), Green Tea

SARS‐CoV‐2 encodes two proteases, the papain‐like protease (PLpro, encoded within nsp3) and 3‐chymotrypsin‐like “main” protease (3CLpro or Mpro, encoded by nsp5). (168) PLpro also has a critical role in antagonizing the host’s innate immunity. (169) PLpro is an excellent candidate for antiviral drug development, as they are not only blocking virus replication but also inhibiting the dysregulation of signaling cascades in infected cells. (170) The papain-like protease PLpro is an essential coronavirus enzyme that is required for processing viral polyproteins to generate a functional replicase complex and enable viral spread. PLpro is also implicated in cleaving proteinaceous post-translational modifications on host proteins as an evasion mechanism against host antiviral immune responses. (171) The PLpro possesses deubiquitinating activity is important in immune regulation. (172)

Role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) papain-like protease protein (PLPro) in COVID-19 infection. SARS-CoV-2 infects cells using host ACE2 and TMPRSS2 receptors. After infection, the virus uses the host transcription machinery and transcribes its early gene containing Non-structural protein (Nsp)1, Nsp2, Nsp3 and Nsp4 as a proprotein. PLPro, a papain like protease (PLP), is autocleaved from Nsp3 protein due to its intrinsic proteolytic function. SARS-CoV-2 PLPro then cleaves Nsp1–Nsp2, Nsp2–Nsp3 and Nsp3-Nsp4 junctions of the proprotein to give rise to the individual proteins. PLPro acts like a deubiquitinase and deISGylation enzyme on endogenous host proteins to abrogate host specific innate immune response. (173)

Zinc (Supplement – avoid nuts during viral infection). Zinc inhibits SARS-CoV papain-like protease 2, which is also a key enzyme for viral replication and assembly of functional viral proteins. (174)

Help Zinc get into cells: (Quercetin)
Quercetin Dietary Sources: Green Tea, Capers, Red Onion, Shallots, Red Apples (Unskinned), Grapes, Berries, Cherries, Scallions, Kale, Cherry Tomatoes (Organic = up to 79% more), Broccoli, Brussels Sprouts, Cabbage, Green & Yellow Bell Peppers, Almonds, Pistachios, Cooked Asparagus, Elderberry Tea

Potential Candidates: (Computer Studies)

ECGC, Hypericin, Rutin, Cyanidin 3-O-glucoside
The dietary compounds (-)-epigallocatechin gallate (ECGC), hypericin, rutin and cyanidin-3-O-glucoside were predicted to bind more strongly to the naphthalene-inhibitor site of the SARS-CoV-2 papain-like proteases than the known inhibitors (in silico). The molecular docking results demonstrated that (-)-epigallocatechin gallate, cyanidin-3-O-glucoside, rutin and hypericin had strong binding affinities. (175)

  • Cyanidin 3-O-glucoside
    The blind docking results on the main PLpro chains showed that these natural ligands had multiple poses within this region (in silico). (176)
    Dietary sources of Cyanidin 3-O-glucoside: Black Grapes, Cranberries, Elderberry, Blackberries, Blackcurrant, Gooseberry, Blueberry, Raspberry, Redcurrant, Strawberry, Nectarines, Peaches, Plums, Cherries, Orange Juice, Pomegranate juice, Black beans, Olives, Red Lettuce (177)
  • ECGC (Green Tea)
    EGCG, a Green Tea Catechin, inhibits PLPro in silico. Catechins present in green tea extract hold much promise in curbing COVID-19 disease pathobiology owing to their multidimensional anti-inflammatory effects in humans and their potential as natural therapeutics with minimal side effects. (178)
  • Hypericin (St. John’s Wort), Rutin (St. John’s Wort & certain fruits and vegetables)
    Rutin is a plant pigment (flavonoid) that is found in certain fruits and vegetables. Rutin is used to make medicine. The major sources of rutin for medical use include buckwheat, Japanese pagoda tree, and Eucalyptus. Other sources of rutin include lime tree flowers, elder flowers, hawthorn, rue, St. John’s Wort, Ginkgo, apples, and other fruits and vegetables.

Ginkgo biloba
Gingkoglide-A, a terpene lactone mainly found in tree Ginkgo biloba was found best against PLpro (in silico). (179)

Luteolin C3/luteolin and C43/abyssinone II were disclosed as potent inhibitors with enhanced binding affinity compared to remdesivir against Mpro/3CLpro, PLpro and ACE2 of COVID-19. (180)
Luteolin Dietary Sources: Oregano, Bird Chilli, Parsley, Onion Leaves (Spring Onion), Celery Seeds, Thyme, Green peppers, Chamomile, Juniper Berries

HCQ
An in silico study anticipates that PLPro is a promising target of CQ and HCQ, and suggests that it needs to be tested. (181)

Mapping out the VIRAL REPLICATION Phase in a Spreadsheet:
(Scroll up/down, left/right for different therapeutics that are implemented in this phase)

Downloads

Viral Replication Targets
View in new window
Download (as PDF)
Dietary sources of Vitamins
View in new window
Download (as PDF)
My Covid Notes (so far)
(Download my notes)

I created another spreadsheet to visualize various therapeutics and what they can target, as well as to collect my references. This gives me a birds-eye view on how each individual therapeutic may work to combat COVID-19, and motivate me to add certain foods to my diet for the extra covid-fighting benefits.

Devices: Fingertip Pulse Oximeter to measure oxygen levels. (Normal reading 95-99, anything less than 93 requires emergency evaluation.)

See: COVID-19 Phases & Targets – to learn more about symptoms of the various stages & for full list of downloadable resources.

Sorry for publishing this post out too early (before it’s finished) but I want to update it on-the-fly to cross-reference with others who are also researching this most critical topic and most critical phase. Come back daily to see updates.

Still to add to this post is information to prevent inflammation and clotting.

References[+]

Penny... on Health
Penny... on Health

DISCLAIMER: The information on this website is not medical science or medical advice. I do not have any medical training aside from my own research and interest in this area. The information I publish is not intended to diagnose, treat, cure or prevent any disease, disorder, pain, injury, deformity, or physical or mental condition. I just report my own results, understanding & research.