Nitric oxide nasal spray for covid-19

kangaSue

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The makers of SaNOtize Nitric Oxide Nasal Spray, which is designed to kill the covid-19 virus in the upper airways, preventing it from incubating and spreading to the lungs, says this is 99.9% effective in lab tests and are now into doing clincal trials.
Nitric oxide blocks ACE-2 receptor essential for the virus to infect cells, destroys Covid mutant variations
Inhaled nitric oxide gas in low concentrations is one of the few treatments that can help for acute lung failure due to covid-19 so I was wondering if maybe snorting the likes of *arginine would have enough conversion to nitric oxide to confer protectioin from covid-19 too.

*possibly arginine pyroglutamate that @Hip has posted about snorting for anxiety before, and has the best blood-brain barrier penetration of the arginine supplements.
https://forums.phoenixrising.me/thr...and-the-nmda-receptor.1460/page-3#post-323656
 

Hip

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The claims sound impressive:
“If you use it daily, I really believe you won’t be affected by Covid-19. We have shown in the clinical trials that the people who used it did not get infected.”
Source: here.

Could not find any info on the ingredients of this nasal spray.

It cannot be nitric oxide itself, as this has a half life of just seconds in the blood. So would have to be some chemicals which manufacture nitric oxide, like the enzyme nitric oxide synthase, which acts on arginine to form NO.
 

kangaSue

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Could not find any info on the ingredients of this nasal spray.
It looks like sodium nitrite citric acid is the active ingredient

Company co-founder Dr Gilly Regev, has said in different media releases that the product (Nitric Oxide Releasing Solution - NORS) is a liquid, made out of compounds that are used naturally in food, and when you combine them together, they create a very small amount of nitric oxide, and that she is confident of its efficacy because pre-Covid, it was being used to treat other diseases such as acne, athlete’s foot and even the flu.

Dr Regev authored a 2013 paper investigating sodium nitrite citric acid as an antifungal agent for tinea pedis (Athlete's Foot) and it's also tagged with the same name of NORS so presumably the same agent for COVID-19 too.

https://pubmed.ncbi.nlm.nih.gov/23082864/
 

Hip

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Company co-founder Dr Gilly Regev, has said in different media releases that the product (Nitric Oxide Releasing Solution - NORS)
Very interesting.

The paper you linked to details NORS:
NORS were prepared utilizing sodium nitrite and citric acid, as described in a prior publication, to achieve a specific production of an effective antimicrobial nitric oxide–free gas concentration which was previously identified in the published patent by Stenzler (Stenzler and Miller 2006; Miller and Regev 2011).

Specifically, this was done by dissolving solid sodium nitrite (NaNO2) into sterile distilled water (dH2O) to reach a final concentration of 1–20 mmol per liter . Then, those solutions were acidified to pH 3.7 using a predetermined mass of citric acid (up to 3 mmol per liter).
So it would be easy enough to make up your own version of NORS. However, acidic compounds placed in the nose can stink like hell, and I wonder if pH 3.7 is too acidic for nasal use. Perhaps the acidity may have to be reduced (less citric acid) if you want to spray it in the nose.
 

kangaSue

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So it would be easy enough to make up your own version of NORS. However, acidic compounds placed in the nose can stink like hell, and I wonder if pH 3.7 is too acidic for nasal use. Perhaps the acidity may have to be reduced (less citric acid) if you want to spray it in the nose.
Can't find details for the UK study but an advanced Canadian phase 2 clinical trial was looking at 3 routes of delivery, Nitric Oxide Gargle (NOG) every morning, Nitric Oxide Nasophyaryngeal Irrigation (NONI) every evening, and Nitric Oxide Nasal Spray (NONS) up to 5 times per day
https://www.clinicaltrials.gov/ct2/show/NCT04337918
 

Mary

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Humming apparently can increase nitric oxide. In the book The Oxygen Advantage, author Patrick McKeown states:

The production of nitric oxide in the nasal sinuses can be increased by simply humming. In an article published in the American Journal of Respiratory and Critical Care Medicine, Drs Weitzberg and Lundberg described how humming increased nitric oxide up to fifteen-fold in comparison with quiet exhalation. They concluded that humming causes a dramatic increase in sinus ventilation and nasal nitric oxide release.
The book actually is quite interesting. I initially had no interest in it and wondered how someone could write an entire book about breathing, but he did. Among other things, the way we breathe has had an effect on causing crooked teeth, all sorts of things.
 

Gingergrrl

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The makers of SaNOtize Nitric Oxide Nasal Spray, which is designed to kill the covid-19 virus in the upper airways, preventing it from incubating and spreading to the lungs, says this is 99.9% effective in lab tests and are now into doing clincal trials.
Company co-founder Dr Gilly Regev, has said in different media releases that the product (Nitric Oxide Releasing Solution - NORS) is a liquid, made out of compounds that are used naturally in food, and when you combine them together, they create a very small amount of nitric oxide, and that she is confident of its efficacy because pre-Covid, it was being used to treat other diseases such as acne, athlete’s foot and even the flu.
This was really interesting to read about @kangaSue and thank you for posting it.

For anyone still interested, Israel gave interim approval for Sanotize's spray, even before the Phase 3 trials. I saw some people successfully being able to purchase it online, although it is quite pricey (USD$45/ 1 month supply): https://www.israelpharm.com/online-pharmacy/enovid/
Thank you for this link @marcjf and I wanted to clarify... @kangaSue or @Hip, is the link to this product "Enovid" from the Israeli pharmacy the same product as "SaNOtize" (the one that kangaSue posted in the first post of this thread)? Also, @Hip are you thinking of trying this product?

I just read through the link in great detail and researched the ingredients and was hoping that @Hip (or anyone else), if you could tell me if I am understanding them correctly. Also, I want to put a disclaimer that I am not endorsing this product or saying that it is effective vs. I just want to learn more about it.

These are the ingredients that it lists:
1) Sodium Chloride
2) Citric Acid
3) HMPC (I'm assuming this is "hyroxy-propyl-methyl-cellulose")?
4) Sodium Nitrite
5) Benzalkonium Chloride

The ingredient that looks the most concerning to me is the sodium nitrate (b/c I think it can cause allergic reactions and is a carcinogen)?

I wasn't familiar at all with the last ingredient, "Benzalkonium Chloride" but Google said that it is an antimicrobial preservative that is in most eye drops so I checked the package for my eye drops that I use daily (called Zaditor) and sure enough, they contain Benzalkonium Chloride!

I'd love to hear any thoughts that anyone has on this product and if anyone is planning to buy it. One downside is that the product has to be discarded within 30-days of opening the bottle.
 

Hip

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@Hip, is the link to this product "Enovid" from the Israeli pharmacy the same product as "SaNOtize" (the one that kangaSue posted in the first post of this thread)? Also, @Hip are you thinking of trying this product?
SaNOtize appears to be the company, and the Enovid COVID nasal spray is one of their products.

Enovid's anti-coronavirus effects look impressive: a double-blind placebo-controlled phase II clinic trial conducted in the UK found that in COVID patients who were already showing symptoms, the spray reduced the viral load by 20 times after 24 hours, and reduced viral levels by 100 times after 72 hours.

That seems to be a large reduction in viral load. Having a spray like this in the cupboard as an emergency treatment if you did get COVID seems like a good idea. It works even once you have already developed COVID.

It could also be used to prevent COVID if you had a high risk exposure, like a visit to a busy indoor restaurant.

There is no data showing that Enovid reduces the chances of hospitalization or death from COVID, but such data would only be obtained from a much larger scale clinical trial.



The sodium nitrite found in Enovid (which incidentally is a preservative found in sausages, bacon and ham) is not itself a carcinogen, but can create carcinogens when it reacts with chemicals in food under the acidic conditions of the stomach. That's why cured meats are slightly carcinogenic. But there would be no carcinogen concern with nasal use.

This sodium nitrite in Enovid reacts with the citric acid in the spray to form nitric oxide (NO), a potently antiviral substance (NO is also naturally produced in the body and in the nasal cavity to fight pathogens).

As far as I can make out, the clever thing about this nasal spray is the use of hydroxypropyl methylcellulose (HPMC), which I had not heard of before, but I think it is being employed as a drug slow release mechanism (here is a study focusing on the slow drug release properties of HPMC). My guess is HPMC stops the sodium nitrite from reacting with the citric acid in the spray bottle, and the facilities a slow controlled reaction of these two ingredients to create NO in the nose once the spray is administered.

There would need to be some agent in the nasal spray bottle to stop the sodium nitrite from reacting with the citric acid, otherwise the NO will be created in the bottle, and the ingredients would be used up before they have a chance to get to your nose.



There are also other antiviral nasal sprays on the market:

VIRALEZE by Starpharma costs £15 and contains the antiviral astodrimer sodium. It has not been though human clinical trials, and the efficacy of astodrimer sodium against the SARS-CoV-2 coronavirus has only been demonstrated in vitro.

Taffix by Israel-based Nasus Pharma costs $56 for four, and appears to create a barrier against viruses, rather than have antiviral effects:
“Taffix is a powder that when it is inhaled covers the nasal passages to create a protective layer around the cells so that the virus cannot reach the receptors cells in the nose.”
Ref: here

So Taffix is I think a spray you would have to use several times daily to prevent coronavirus infection. But it is not clear if it would help once you have caught coronavirus. One observational study suggested it does have COVID preventative effects if used daily.

Taffix uses the same hydroxypropyl methylcellulose (HPMC) found in Enovid, but I believe in this case the HPMC is being employed as the protective barrier.

ViroStop by Herb-pharma AG costs £14, and contains a special extract obtained from Cistus creticus. It works by creating a protective barrier against viruses.
 
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Gingergrrl

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SaNOtize appears to be the company, and the Enovid COVID nasal spray is one of their products.
Thank you for clarifying this @Hip and I was not certain if I was understanding it correctly. I really appreciate all of the detailed info that you put in your post above.

Enovid's anti-coronavirus effects look impressive: a double-blind placebo-controlled phase II clinic trial conducted in the UK found that in COVID patients who were already showing symptoms, the spray reduced the viral load by 20 times after 24 hours, and reduced viral levels by 100 times after 72 hours.
It looked very impressive to me as well but your confirmation is very helpful. I am continuing to research this product and it seems like different aspects of it (including the development, research, trials, etc) have been done in Canada, the UK & Israel which is very impressive.

That seems to be a large reduction in viral load. Having a spray like this in the cupboard as an emergency treatment if you did get COVID seems like a good idea. It works even once you have already developed COVID.

It could also be used to prevent COVID if you had a high risk exposure, like a visit to a busy indoor restaurant.
This is exactly what I was trying to sort out in my head: if this product not only reduced viral load in someone AFTER they have developed COVID or if it was also a preventative or prophylactic if someone had been exposed to COVID (and this could prevent the person from getting infected).

It sounds like from what you are saying, that it could potentially do both.

The sodium nitrite found in Enovid (which incidentally is a preservative found in sausages, bacon and ham) is not itself a carcinogen, but can create carcinogens when it reacts with chemicals in food under the acidic conditions of the stomach. That's why cured meats are slightly carcinogenic. But there would be no carcinogen concern with nasal use.
That is interesting and I knew that both nitrates & nitrites could be found in cured meats (which I don't eat b/c of allergic reactions w/MCAS). My late mom also could not eat any food product with nitrates or nitrites b/c it made her very sick and gave her severe chest pain. I had also always heard that they were a carcinogen so I avoided them all together.

But it sounds like you are saying that the nitrates & nitrites must be combined w/meat in order to become a carcinogen? Do you think that the nitrates in this nose spray would cause an allergic reaction (or do you think that an allergic reaction also comes from the combination of the nitrates with food)? Last, are "nitrates" and "nitrites" the same thing or two different things?

As far as I can make out, the clever thing about this nasal spray is the use of hydroxypropyl methylcellulose (HPMC), which I had not heard of before, but I think it is being employed as a drug slow release mechanism (here is a study focusing on the slow drug release properties of HPMC). My guess is HPMC stops the sodium nitrite from reacting with the citric acid in the spray bottle, and the facilities a slow controlled reaction of these two ingredients to create NO in the nose once the spray is administered.
I thought that was interesting, too, and thank you for explaining it further!

Thank you for this additional into, too!
 

Hip

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Last, are "nitrates" and "nitrites" the same thing or two different things?
They are related chemicals but not the same. Nitrate chemical formula = NO3 whereas nitrite = NO2 (one oxygen atom less). But nitrates can be converted into nitrites in the body, by bacteria. And then it is the nitrites which can react with food to create carcinogens.

Nitrates are naturally found at high levels in foods like beetroot juice. Nitrates can lower blood pressure (so drinking beetroot juice can lower blood pressure).



Do you think that the nitrates in this nose spray would cause an allergic reaction
I am not sure, but if you can tolerate ham, bacon or sausages, which contain nitrite, then I would imagine you'd be fine with this spray.

Interestingly, the hydroxypropyl methylcellulose (HPMC) contained in the Enovid and Taffix nasal sprays, which is also called hypromellose, is actually the active ingredient in anti-allergy nasal sprays. It forms a protective coating in the nasal passages which protect from allergy.

This same protective coating also blocks viruses, which is how the Taffix nasal spray works. I imagine the Enovid nasal spray will also work by this hypromellose protective coating mechanism, but in addition works by generating NO in the nose which is antiviral.

You could probably buy a cheaper anti-allergy nasal spray that was based on hypromellose, and get a similar protection from viruses that Taffix provides.

Though I am not sure if Taffix will help fight viral infection in the nose once you have caught coronavirus. From what I have read, it is sold as a prevention for COVID, rather than a treatment for COVID.

In one group of high risk people given Taffix, it reduced the incidence of COVID from 10% in those not using the spray, to 2.4% in those who used it. Ref: here

So Taffix appears to reduce your chances of catching COVID by a factor of 4. You would have to remember to apply it before a risky exposure for it to work though. And you are recommended to apply it 3 times daily if you want all-day protection.
 

Gingergrrl

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Nitrates are naturally found at high levels in foods like beetroot juice. Nitrates can lower blood pressure (so drinking beetroot juice can lower blood pressure).
Do you think this Enovid product would lower blood pressure (or is the amount too small)? I was curious b/c my BP runs chronically low to begin with.

I am not sure, but if you can tolerate ham, bacon or sausages, which contain nitrite, then I would imagine you'd be fine with this spray.
In general, I don't eat pork or red meat and definitely have not tried any meat products w/nitrates since I developed MCAS. Even though my MCAS is in remission now, I still avoid things that could trigger a reaction. I sometimes buy sliced turkey but only the kind that is free of nitrates/preservatives (so to answer your question, I am truly not sure)!

Interestingly, the hydroxypropyl methylcellulose (HPMC) contained in the Enovid and Taffix nasal sprays, which is also called hypromellose, is actually the active ingredient in anti-allergy nasal sprays. It forms a protective coating in the nasal passages which protect from allergy.
That is interesting.

You could probably buy a cheaper anti-allergy nasal spray that was based on hypromellose, and get a similar protection from viruses that Taffix provides.
If I end up ordering the product, I would order the Enovid (and would want to try the real thing vs. try to create a cheaper version that hasn't been researched or studied re: COVID).
 

Hip

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Do you think this Enovid product would lower blood pressure (or is the amount too small)? I was curious b/c my BP runs chronically low to begin with.
I would not have thought so, a nasal spray pump dose only contains a tiny amount of nitrate.
 

Wayne

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Just ran across the following. I wonder if putting raw honey in our nostrils would be protective. I've heard it's great for sore throats.

"Raw honey contains nitric oxide metabolites that are converted back to nitric oxide when consumed. Research shows honey increases nitric oxide and total nitrite concentrations and improves endothelial function. Heating decreases the nitric oxide metabolites in the honey..."
 

Wayne

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One way to raise Nitric Oxide levels in the body is to consume some organic beet root juice powder (I mix this in with my smoothies). Whether or not it might help prevent COVID infection, I can't say. But I sure feel better since regularly using this and other organic juice powders, like wheatgrass, celery, pineapple, tart cherry, etc. It's considerably improved my digestion.


Organic Beet Root Juice Powder - All Natural Nitric Oxide Booster Supplement - Support Long Lasting Endurance - Great Pre or Post Workout Drink Mix - Raw, Gluten Free, Non GMO, Vegan, & Kosher - 1 lb
 

Hip

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@Gingergrrl , I just want to add a qualifier to the above analysis of the Enovid nitric oxide nasal spray for COVID:

The study found a 20-fold reduction in coronavirus RNA just 24 hours after starting Enovid nasal spray treatment.

I originally assumed the 20-fold reduction was measured in the blood. However, I've just now realized this 20-fold reduction in viral RNA was measured by nasal and throat swabs, not in the blood. Well, you would expect nasal and throat viral RNA levels to decrease, as that is the area where the antiviral spray is applied.

Whether there is a corresponding reduction of viral load in the blood, I am not sure. I am not sure how nasal and throat levels correlated to blood levels.

So I may have over-rated this nitric oxide nasal spray; it may not be as useful as I first thought.

If the spray could cause a 20-fold reduction in viral RNA in the blood, that would be something, as that might have wider benefits, protecting you from developing a lung infection with coronavirus.

But if the 20-fold reduction is only in the nose and throat, that may not be as good.
 

Wayne

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But if the 20-fold reduction is only in the nose and throat, that may not be as good.
My understanding is it takes COVID anywhere from 24 to 72 hours to migrate from the nose and throat down into the lungs. If that's the case, it would seem that a 20-fold reduction in viral load in the nose and throat would be a phenominal preventative measure. If used on a daily basis, it would seem nobody would end up with a COVID infection that could get established in the lungs or rest of the body.
 

Hip

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My understanding is it takes COVID anywhere from 24 to 72 hours to migrate from the nose and throat down into the lungs. If that's the case, it would seem that a 20-fold reduction in viral load in the nose and throat would be a phenominal preventative measure.
It could pan out like that, I agree; but I think without testing this nasal spray on a larger group, it's hard to say whether it might actually reduce hospitalization and death.

Most people I think would only start using the spray once symptoms appeared, given the cost of the spray (it would be quite expensive if you used it daily when healthy).

So maybe by that time it's too late: the virus may have already spread to the heart or lungs.

Of course, reducing the viral load in the nose and the throat even at a later stage might still help reduce the severity of a COVID lung infection, as it may prevent later stage translocations of virus from nose and throat to lungs.
 

Gingergrrl

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@Gingergrrl , I just want to add a qualifier to the above analysis of the Enovid nitric oxide nasal spray for COVID:
If the spray could cause a 20-fold reduction in viral RNA in the blood, that would be something, as that might have wider benefits, protecting you from developing a lung infection with coronavirus. But if the 20-fold reduction is only in the nose and throat, that may not be as good.
Thank you @Hip for the additional analysis and info. I am still deciding if I want to purchase the Enovid spray but probably will b/c I see no downside to having it (even if I never end up using it).

My understanding is it takes COVID anywhere from 24 to 72 hours to migrate from the nose and throat down into the lungs.
@Wayne I was curious if you have seen any studies to back this up? I am not whatsoever saying that you are wrong vs. that I have no idea how long it takes the COVID virus to travel from the nose/throat to the lungs and would love to see more info (if you have any).

Most people I think would only start using the spray once symptoms appeared, given the cost of the spray (it would be quite expensive if you used it daily when healthy).
Do you think the spray might act as a preventative if someone used it in advance of being in a high risk situation (in a crowd of people or in a situation where others were not wearing masks)? Also, in a situation in which someone learned very quickly that they had just been exposed to someone with COVID (but they did not yet have any symptoms themselves).

Of course, reducing the viral load in the nose and the throat even at a later stage might still help reduce the severity of a COVID lung infection, as it may prevent later stage translocations of virus from nose and throat to lungs.
That makes sense to me (but do not know what the statistics are about this).