How Does Hydroxychloroquine Work for Coronavirus - Why It May Be a Game-Changer

How does hydroxylchloroquine work for coronavirus covid19 and sars

 

First, some background is in order.

 

When we first started watching what was happening in China, we realized right away this was something different.

 

Here's why.

 

Increasing the average standard of living for Chinese people is really the only basis for the government to hold its power.

 

That's been the agreement for a few decades now.

 

We'll overlook the various negatives of the rule if you just make us richer each year on average.

 

For the government to shut down the one thing that brings them legitimacy means the alternative was horrendous. 

 

You can't trust what they say...only what they do.

 

We were not surprised by how dire it's looking right now (March 21st) and we fully expected months of this at best.  Maybe years taking into account the nature of viruses (mutations, cycling, etc).

 

Then came hydroxychloroquine.

 

A review of this very old and established drug's effect on coronavirus from an esteemed researcher in Aix En Provence, France was groundbreaking.

 

We'll look at that study below but more importantly, what on earth is a malaria drug doing in the body to combat coronavirus?

 

It's an interesting bit of microscopic sleuthing.

 

The key is this...hydroxychloroquine has the potential to quickly (already inexpensive, studied, and readily available) relegate coronavirus to just being a bad cold.

 

That totally changes the dynamics of where we are since so much of the fear and panic (and sheltering in place) is about the unknown...can I DIE from coronavirus?

 

Take that away and we'll quickly come out of this.  Relatively speaking.

 

So...what is hydroxychloroquine and how does it really work?

 

We should probably understand the simple substance that just might save the world.

 

More importantly, we'll look at a safe and available (for now) supplement that mirrors a key pathway of hydroxychloroquine below.  That may be the biggest takeaway.

 

We'll cover these areas: 

  • What is hydroxychloroquine
  • How does hydroxychloroquine work for coronavirus
  • Is hydroxychloroquine safe
  • Other antiviral supplements

 

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Let's get started.  We need to ask our doctor about this one.

What is Hydroxychloroquine 

It's a pretty old drug (approved in 1955 originally) that gained popularity for soldiers returning to the US from areas prone to malaria.

 

Chloroquine was the original drug but researchers discovered that by adding a hydroxyl group to it, the toxicity was reduced:

Hydroxychloroquine (HCQ) sulfate, a derivative of CQ, was first synthesized in 1946 by introducing a hydroxyl group into CQ and was demonstrated to be much less (~40%) toxic than CQ in animals 

https://www.nature.com/articles/s41421-020-0156-0

 

It's on the WHO's list of safest and most effective medications needed in a health system.

 

These days, hydroxychloroquine has two different uses: 

  • Anti-malarial agent
  • Autoimmune medication (like for rheumatoid arthritis or Lupus, etc)

 

The pathways for both of these are interesting in terms of coronaviruses in general and the whole SARS (Severed Acute Respiratory Syndrome) family of which COVID19 appears to be a related cousin.

 

The two pathways in question are as follows and we'll get into specifically below: 

  • Hydroxychloroquine raises the PH (acid/base measurement) level in the specific parts of the cell that govern genetic replication - we'll see why this is important for coronavirus below.
  • Hydroxychloroquine calms the immune response (specifically TLR4 which responds to bacteria) which speaks to its effects on Lupus and Rheumatoid arthritis

 

Okay...that's all a mouthful if you're not daily into virus and immune biology.

 

Let's drill down into these further and understand why any of this matters for coronavirus or SARS.

How does hydroxychloroquine work for coronavirus 

Let's get a quick understanding of what the viruses need to thrive (so we can choke that out!) and why Covid19 is different.

 

First, what makes the current coronavirus so different.

 

Keep in mind that coronaviruses are a common class of virus that we come into contact every year.

 

It's estimated that the average person has 3-4 different infections with coronaviruses each year.

 

Usually, we just have a common cold with mild symptoms.

 

What makes SARS and its newest rendition, Covid19 so difficult?

 

Two aspects.

 

First, there appears to be a difference in its "spike", the little hooks that project from the center circle which makes it very effective at accessing our ACE2 receptors.

 

Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus (CoV) designated SARS-CoV. The virus utilizes angiotensin-converting enzyme 2 (ACE2) as the primary receptor. 

 

https://www.ncbi.nlm.nih.gov/pubmed/17715238

 

This is important if you look at the primary cause of death which is acute pneumonia or the lungs being overwhelmed by both virus and our immune response.

 

ACE2 receptors are primarily in our cardiovascular system within the epithelial layer (the "skin" of our plumbing system) with the lungs being the major player there.

 

These receptors are for angiotensin - the chemical that constricts arteries and blood flow.

 

That's why we have classes of blood pressure medications that block, suppress, or otherwise interfere with this pathway.

 

Covid19 and SARS have an improved ability to access our cells via this ACE2 receptor. 

  • The second "gain of function" that makes covid19 not your average is cold is a trick it borrowed, stoled, or was engineered (hey, China's only level 4 lab is 19 miles from the "wet market" in Wuhan...of all the jin joints) which is similar to HIV. 
  • It involves being able to access a key genetic slicer and dicer called furin.
  • The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. 

https://www.sciencedirect.com/science/article/pii/S0166354220300528?via%3Dihub

 

This is very odd for coronaviruses and its usually found in other very dangerous viruses: 

For example, the envelope proteins of viruses such as HIV, influenza, dengue fever, SARS-CoV 2[13] and several filoviruses including ebola and Marburg virus must be cleaved by furin or furin-like proteases to become fully functional. 

https://en.wikipedia.org/wiki/Furin

 

Okay...so know thy enemy.

 

Let's get back to hydroxychloroquine, please.

 

Before we get into the studies of hydroxychloroquine and SARS or Covid19, let's understand how it's thought to affect viral replication.

 

We'll try not to go too deep into the weeds but this is fascinating work on an ancient enemy.

 

First, we need to introduce the coronavirus means of operation.

 

Once it gains access to our cell (via the spike mentioned above), it takes control of our cellular machinery to make more of it.

 

Coronaviruses primarily carry out this work in our endosomes within cells.

 

The endosome is like a sorting and packing warehouse for the cell.

 

There's a whole pathway through these endosomes from early to late endosome (not terribly creative naming construct).

 

The output from the endosome then goes out to the lysosome where it's generally excreted.

 

There's is a great breakdown and visual of this process here: 

https://viralzone.expasy.org/992?outline=all_by_protein

 

The interesting piece is this...it's a very PH controlled environment.

 

This means the PH level (acid to base balance) directly affects behavior in these different sections (early and late).

 

Why on earth are we going into all of this?

 

The key takeaway to understand hydroxychloroquine's effect is this: 

The specific trigger depends on the virus and very often involves the exposure to the low pH of the late endosome. 

https://viralzone.expasy.org/992?outline=all_by_protein

 


A primary effect of hydroxychloroquine is to raise the PH levels in the endosome (and elsewhere within a cell): 

Both CQ and HCQ are weak bases that are known to elevate the pH of acidic intracellular organelles, such as endosomes/lysosomes, essential for membrane fusion. 

https://www.nature.com/articles/s41421-020-0156-0

 

Just an FYI, "membrane fusion" is how the virus breaks into the cell.

 

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Studies have actually measured the effects of this PH rise on the SARS machinery through our endosomes and lysosomes.

 

Don't worry...we'll decipher the Klingon afterward: 

By contrast, in the presence of CQ or HCQ, significantly more virions (35.3% for CQ and 29.2% for HCQ; P < 0.001) were detected in the EEs, while only very few virions (2.4% for CQ and 0.03% for HCQ; P < 0.001) were found to be co-localized with LAMP1+ ELs (n > 30 cells) (Fig. 1b, c).  

https://www.nature.com/articles/s41421-020-0156-0

 

CQ is chlorquine. HCQ is hydroxycloroquine.

 

Basically, what they found is that viruses were not making it through the PH gauntlet along the endosome assembly line (from EE early endosome to EL late endosome).

 

Inputs were going into the early endosome but not coming out the back end.

 

A 10 fold reduction! (29% on the front end - 2% on the back end).

 

We're killing the coronaviruses' ability to replicate with PH!

 

Remember how the coronavirus requires the low PH of the late endosome?

 

You now know why hydroxychloroquine works.

 

Just to refresh on its effects within the cell: 

This increases the pH of the lysosome from 4 to 6.[23] Alteration in pH causes inhibition of lysosomal acidic proteases causing a diminished proteolysis effect. 

https://en.wikipedia.org/wiki/Hydroxychloroquine

 

There's a secondary effect of hydroxychloroquine on the spike of the coronavirus.

 

In addition, CQ could inhibit SARS-CoV entry through changing the glycosylation of ACE2 receptor and spike protein 

https://www.nature.com/articles/s41421-020-0156-0

 

There's that ACE2 receptor.  Glycosylation is the key code to gain entry to a given cell.

 

Remember that SARS and covid19 have an upgrade where they were given the keycode to our ACE2 receptors...come on in!

 

Chloroquine (and by default, hydroxychloroquine) reset the code so to speak.

 

We just looked at two key effects of hydroxychloroquine and SARS or covid19.

 

Let's now zoom 30,000 feet up to see the net effect of all this machinery and PH tampering.

Hydroxychloroquine and Sars, Covid19, and coronavirus studies 

SARS came first so let's start there.

 

We have recently reported that two drugs, remdesivir (GS-5734) and chloroquine (CQ) phosphate, efficiently inhibited SARS-CoV-2 infection in vitro 

https://www.nature.com/articles/s41421-020-0156-0

 

We covered Remdesivir and coronavirus in detail here but it will take longer to get in the pipeline compared to hydroxychloroquine.

 

Needless to say, the Covid19 pandemic brought new attention to hydroxychloroquine.

 

First, studies in the lab on covid19 infected cells: 

A dose-dependent decrease in virus antigen-positive cells was observed starting at 0.1 μM chloroquine, and concentrations of 10 μM completely abolished SARS-CoV infection.  

https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-2-69

 

Interestingly, they found a preventative effect when administered before Covid19: 

pretreatment with 0.1, 1, and 10 μM chloroquine reduced infectivity by 28%, 53%, and 100%, respectively.

 

Separately, they found that treatment AFTER infection with hydroxychloroquine reduced the ability to infect other cells afterward.

 

When chloroquine was added after the initiation of infection, there was a dramatic dose-dependent decrease in the number of virus antigen-positive cells 

 

The antigen-positive cells is key to the pandemic.  

 

Essentially, when an infected person gets released as "cured" and not infections, it's a negative read for these antigen-positive cells.

 

Finally, the study that really opened everyone's eyes including our government.

 

French study on hydroxychloroquine and Covid19

 

Their results: 

Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration  

https://www.mediterranee-infection.com/wp-content/uploads/2020/03/Hydroxychloroquine_final_DOI_IJAA.pdf

 

Interestingly, when they added azithromycin, a common antibiotic (z-PAC), the results were significantly improved.

 

Why on earth would an anti-biotic affect Covid19?

 

Turns out that it's had long-known antiviral effects in a specific area of interest.

 

The epithelial lining of the lungs! (where the ACE2 receptors are prevalent).

 

It's effect?

 

Azithromycin pre-treatment reduces RV replication in CF bronchial epithelial cells, possibly through the amplification of the antiviral response mediated by the IFN pathway.  

https://erj.ersjournals.com/content/45/2/428

 

IFN is the key there.  Interferon, our body's natural antiviral (it gums up their system).

 

We looked at CBD and interferon (boosts it) at our CBD and immune response review.

 

Just look at the chart when hydroxychloroquine and azithromycin is combined: 

https://www.mediterranee-infection.com/hydroxychloroquine-and-azithromycin-as-a-treatment-of-covid-19/

 

Now you see why this is a deal-breaker?

 

Most importantly, these are both well-studied, easily accessible, and cheap.

 

It's almost a blessing that mother nature (via lots of research) has given us.

 

This is why we're so hopeful for a few months out.

 

Let's look at safety first.

Is hydroxychloroquine safe 

It's listed by the WHO on the list of safe and highly effective medications.

 

So...what are we looking at.

 

First, the course of treatments referenced in the studies above are generally short term.  

 

Studies references here were for 400 mg twice daily the first day followed by 4 days at 200 mg given twice daily of hydroxychloroquine.

 

The french group gave 200 mg 3x's daily for 10 days.

 

A course of days.

 

The main side effect that's more serious deals with the eyes...primarily the retina but this is generally with long term use or very high dosages.

 

Keep in mind that millions of people take this medication for rheumatoid arthritis and lupus (aside from malaria).

 

In fact, most of the side effects (found here) are based on long term use for the autoimmune diseases...not short term acute durations like for covid19 treatment.

 

Azithromycin is even more established in terms of safety.

 

In terms of hydroxychloroquine versus chloroquine: 

Hydroxychloroquine clinical safety profile is better than that of chloroquine (during long-term use) and allows a higher daily dose [13] and has fewer concerns about drug-drug interactions  

https://www.mediterranee-infection.com/wp-content/uploads/2020/03/Hydroxychloroquine_final_DOI_IJAA.pdf

 

In addition, hydroxychloroquine was found to have a better antiviral effect for SARS: 

Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than chloroquine (EC50=5.47 μM) in vitro.  

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa237/5801998

 

Make sure to work with your doctors (there's already a spike in prescriptions above the standard autoimmune requirements) in terms of interactions with other medications.

 

In the meantime, some other key tools to look at.

Other antiviral supplements 

We covered some key supplements that have documented antiviral effects at our CBD and antiviral supplements for immune response review here.

 

The quick takeaways: 

  • CBD - boosts interferon pathway, calms "cytokine storm" (like hydroxychloroquine), and supports immune removal of infected cells (called apoptosis) 
  • Elderberry - reduces viral replication and helps with respiratory function especially early on
  • Ginger - reduced duration and offset cytokine storm
  • Quercetin - reduced viral infection for H1N1 and support of glutathione pathway (see CBD and glutathione)

 

Rounding out these safe options, you have turmeric, high vitamin C, and zinc.

 

Let's focus on that one as we promised above.

 

Quercetin, aside from it many other powerful effects on longevity, cancer, metabolism, etc has a unique trick up its sleeve which it shares with hydroxychloroquine.

 

It's able to transport zinc across our cell's membrane which may drive up the PH so covid19 can't replicate correctly!

 

Check out our full review on supplements that mirror hydroxychloroquine's effect here.

 

Very exciting...cheap, available (for now), and safe.

 

So...do you see why we're cautiously optimistic now?

 

Yes, the next few weeks are going to look really really bad.

 

Once we have double-blind, placebo studies on the hydroxychloroquine and Covid19, it's going to be a game-changer.

 

Removing the fear of death changes everything and we can go back outside and get back to work.

 

Till then, look at the antivirals listed here and take care of each other.  Be safe and be well.

 

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Always work with a doctor or naturopath with any supplement!

The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.

4 comments

  • Thanks Karnig. There are trials happening around the world right now so we look forward to more research! Also, check out the review other supplements that share a key pathway: https://indigonaturals.net/blogs/news/supplements-that-share-a-key-pathway-with-hydroxychloroquine-for-coronavirus

    IndigoNaturals
  • Thanks Bernard. It’s very interesting. Check out this review of a supplement that shares a similar pathway as hydroxychloroquine here: https://indigonaturals.net/blogs/news/supplements-that-share-a-key-pathway-with-hydroxychloroquine-for-coronavirus

    IndigoNaturals
  • Thank you for a very informative piece. I admit that some of the information is above my head.
    From what I did understand, I feel that we are going in the right direction. I do realize that it will take time to test and make sure that the cure does what it is supposed to do.
    As you put it…this could be a game-changer, thanks to the extensive research being done.

    Karnig Thomasian
  • Thanks for the excellent article. It explains a lot.

    Bernard Winiewski

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