Potential Antivirals With NIH Research - A Focus on Safety and Effectiveness
First, an important point. The FDA has not approved or tested CBD for coronavirus or Covid19. We're only going to look at pathways affected by CBD on immune response to viral infection in research only.
Our knee jerk reactions to any viral outbreak belie a simple fact.
It's a virus.
The vast majority of the population will get it at some point or at least until we reach the 60-70% herd immunity level.
That's the nature of a virus...which makes bacteria look colossal in size.
They are operating somewhere in the world at any given time and can re-start from there.
Basically every time you re-open?
The latest viral scare and its slightly altered (mutated) progeny will be circulating somewhere in the world...likely among millions of people.
Eventually, we'll need two things:
- A simple way to remove the lethality of a given viral family
- Safe and effective tools to boost our immune response to these viruses when needed
Besides eating well, exercise, and proper sleep...are there supplements that have a benefit in supporting our immune system along the various stages of viral progression?
Now, take that list and only focus on those with the greatest safety profile since we're all dealing with different genetics and health situations.
Let's get to that list!
We'll cover these from best to less here:
- A quick primer on the new SARS class of viruses and its specific attributes
- Quercetin and anti-viral effects
- NAC and anti-viral effects
- High dose Vitamin C and anti-viral effects
- CBD and anti-viral effects
- Ginger and anti-viral effects
- Elderberry and anti-viral effects
- Yes, there are many other supplements that have antiviral effects (EGCG, licorice, etc) but they also carry a more complicated safety profile.
We want effective AND very safe. Luckily, there are candidates with both.
First, know thy enemy.
A quick primer on the new SARS class of viruses and its specific attributes
First, we need to look at what makes the new SARS class of viruses different.
Let's deal with the whole "It's just the flu" question.
There's a great amount of "fog of war" around how many people actually have it since many don't get tested and even more may not show symptoms at all.
That makes determining a "death rate" almost impossible since we don't really know the denominator.
Back in March, when China said everything was "fixed" we would watch city congestion in real-time to get a sense of whether people were really getting back to life.
So...what's the equivalent with a viral outbreak?
ICU beds and deaths.
If a viral outbreak was not much worse than the flu, we wouldn't see the hospital overrun.
After all, we have flus run through our healthcare system every year and we're not running out of ventilators or ICU beds.
So..this class IS different.
Why and how? This helps with the antiviral selection below believe it or not.
Here are some key points:
- SARS class of viruses has an improved ability to access ACE2 receptors (we'll explain below)
- SARS specifically needs the low PH environment of the late endosome (again, stay with us...we'll explain later)
- SARS class of viruses appear to affect T cells early in the process and result in a "cytokine storm"
- The newest addiction to the SARS class of viruses
- Let's look at each of these since they're partially why this isn't just your father's flu.
SARS class of viruses have an improved ability to access ACE2 receptors (we'll explain below)
Research is showing that these new viruses have an improved "spike" attached to the ACE2 receptor.
ACE2 is where cells interact with angiotensin, the substance our body uses to tighten the inner "skin" (epithelial) inside our cardiovascular system.
We see signs of this improved ability in many ways:
- The lungs get impacted (ACE2 receptors are prevalent in lungs and heart)
- Blood pressure meds which target ACE2 are shown to be a risk (ACE2 inhibitors, ARB's, etc)
This flows into both the infectiousness (coughing "sheds" virion from the lungs) and fatality (viral pneumonia is the leading cause of death).
Next up, new research on how the SARS virus replicates.
SARS viruses needs the low PH environment of the late endosome (again, stay with us...we'll explain)
By now, we've all heard of hydroxychloroquine (don't worry, it will be a household name regardless of how we butcher its name and spelling).
Why on earth is an anti-malarial drug having a potential effect on a virus?
Essentially, hydroxychloroquine transports zinc across the cell membrane and raises the PH (base/acid ratio) within key machinery of the cell.
The very machinery that SARS viruses use to make more of themselves.
In fact, they have a favorite spot called the late endosome where PH levels are nice and low.
When hydroxychloroquine raises this PH, it can drop the virus production by 10 fold!
Check out the review. Also, there is a supplement below which might mirror this same zinc effect with a great safety profile. We'll look at that below.
Now, let's look at how our immune system responds (or over-responds).
SARS class of viruses appear to affect T cells early in the process and result in a "cytokine storm"
It may not be the virus that kills you but your own immune response.
Two things are unique about the SARS class of viruses.
Early research pointed to a drop in T cell formation at exactly the point where they should be ramping up.
T cells are master controllers in our immune system to fight infection.
They initiate a host of other weapons called cytokines.
This is suspiciously similar to HIV which targets the T cell pathway.
In fact, there are proteins in the SARS viruses that are similar to HIV which is why many HIV drugs may help (see review on how Remdesivir works for viruses).
The net result is an explosion in virions (the tiny individual units of a virus) in critical systems (lungs and heart).
The immune system panics and unleashes all hell. Scorched earth.
The well-named "cytokine storm".
We did a full review on CBD and cytokine storm here.
Finally, a quick look at the family tree.
The newest family member to the SARS class of virus
We can look at the SARS family for other hints in terms of antiviral effects since the original SARS has been around for years now.
Members of the SARS family all have similarities.
- They are all from the coronavirus family
- They all primarily operate in the respiratory system
- They all appear to need the late endosome
- They all result in the cytokine storm effect
The difference is that the recent addition to this family can have other "gain of functions".
- It can transmit asymptomatically (without showing symptoms)
- It appears to be more contagious (the improved "spike" for entering ACE2 receptors)
The net effect is this...a good percentage of the population will...strike that...needs to get it or have antibodies (via vaccines, etc) before we can move on with our daily lives.
This so-called "herd immunity" is generally around 60-70% of the population.
The key then is to reduce the fatality of SARS viruses. After all, there are already slightly different versions out there...it can mutate.
Viruses are very sloppy translators of genetic code and they make mistakes all the time.
Our own DNA is littered with the replicating zombie code of viruses from millennia ago.
A vaccine for SARS viruses may look like our flu vaccine which at best, deals with 30% of the flu strains in any given year.
Again, these viruses will likely become a returning albeit, less dangerous, visitor for years.
So....how do we support our immune response to viruses in general.
Let's jump into the supplements starting with the most promising for SARS viruses specifically.
Quercetin and Viral Response
Quercetin had many benefits long before viral interactions came around.
It's a huge supporter of our detox system primarily for glutathione (see CBD and glutathione).
This has knock-on effects for cancer, aging, and just about every system in the body tied to health.
Check out our review of fisetin (its cousin) to understand better.
It's the effect on a particular pathway that is unique and one shared with hydroxychloroquine.
They both are zinc ionophores.
This means that they carry zinc across the cell membrane and raise the PH within the cell.
Remember how SARS viruses need the low PH environment of the late endosome to replicate?
Both hydroxychloroquine and quercetin raise the PH. Hydroxy was shown to block viral replication by 10 fold as a result via this mechanism.
Quercetin has the same mechanism.
Studies are showing that it's about 35% effective in this regard so the 400 mg hydroxy reflected in the studies out of Aix-en-Provence would equate to about 1000 mg of quercetin.
Luckily, that's right in the standard dosage (generally 2 x 500 mg per day).
To be clear, quercetin has NOT been studied in regards to Covid19 or SARS viral infections!
We're just looking at shared pathways.
EGCG (extract from green tea) has the same effect but the safety profile is not as strong as quercetin.
Quercetin's safety profile is one of the best for supplements which is critical.
We did a full review on quercetin sharing a pathway with hydroxychloroquine here with all the NIH studies.
NAC and the SARS class of viruses
Most people are not familiar with NAC but they should be.
Short for N-acetylcysteine, NAC is another big supporter of our detox pathway (the glutathione one mentioned above).
NAC is a precursor of L-cysteine that results in glutathione elevation biosynthesis.
That's just the start.
It has another interesting effect as a mucolytic drug.
Basically, it reduces mucous! (keep in mind for other colds, flus, etc).
This can be critical for ARDS (Acute respiratory distress syndrome).
That's basically the horrific stories pouring out on viral interactions where people feel like they're drowning and they can't breathe.
Hence all the need for ventilators.
A study looked at the effects of NAC on patients with ARDS and ICU duration (not from Covid19):
duration of intensive care unit (ICU) stay in the NAC group was shortened [weighted mean difference (WMD), −4.56; 95% CI: (−7.32 to −1.80); P=0.001].
These are severe patients with lung injury as a result of heart disease (a critical risk for SARS viruses by the way).
NAC is showing benefit is calming the lung damage associated with COPD, asthma, bronchitis, and other ailments that mimick what's happening with severe viral infection.
For example with asthma-related damage (which is telling since it's an over-responsive immune reaction):
Studies showed the preventive effect of NAC antioxidant on the AHR and steroid-resistant accumulation of inflammatory cells in the airways of the animal model with acute exacerbation of asthma.
Remember, it's not the virus that kills us (usually) but the collateral damage from its battle with our immune system:
Many studies have shown that oxidative stress is important in the pathogenesis of pulmonary damage during influenza virus infections.
The researchers looked at NAC in combination with an antiviral drug for a lethal flu infection in mice:
NAC alone was slightly effective (20%) since a suboptimal treatment was used. Survival increased to 60% with Oseltamivir and to 100% with Oseltamivir and NAC used in combination.
The net effect was that the antiviral interfered with the viruses' ability to replicate (like hydroxychloroquine and quercetin above) while NAC soaked up the damage from the viral infection.
A quick lay of the land.
Viruses like the SARS group require a drop in a specific class of chemicals called sulfhydryl groups:
Many viruses require reduced sulfhydryl groups for cell fusion and entry. Coronaviruses, including SARS-CoV-2 (the cause of the condition now named coronavirus disease 2019 or COVID-19), are rich in cysteine, which residues must be intact for viral activity. Sulfhydryl groups are vulnerable to oxidation.
Virus and immune system battle causes mass amounts of oxidative stress (being the primary way that our immune system kills off infected cells).
This eats up sulfhydryl groups.
Drop-in these groups lets the virus replicate more efficiently
These sulfhydryl groups are called thiols….the very thing that gives garlic it's strong odor (and skunks for that matter).
It's also why garlic can have antiviral effects!
Back to NAC.
What is its connection to this whole pathway?
N-acetylcysteine (NAC) is a thiol-containing compound that is able to interfere with redox transitions of thiols and, thus, in principle, able to modulate redox signaling.
It's the very thing that viruses like the SARS family don't like!
This is also critical to SARS viruses gaining entry to our cells, to begin with:
Thus, in contrast to various viruses including HIV (human immunodeficiency virus) examined in parallel, the functions of the SARS-CoV Spike glycoprotein exhibit significant and surprising independence of redox state, which may contribute to the wide host range of the virus.
NAC literally contains thiols!
We know that was a lot to take in.
NAC also has a very strong safety profile which is our 2nd requirement.
Also check out our full review on NAC's research for mental health here.
Next up...a similar pathway from an old friend.
High dose Vitamin C and SARS viral infections
Remember how the media said that Vitamin C was snake-oil?
Turns out they were wrong.
There have been many studies on the effects of vitamin C such as this one for upper-respiratory viral infections:
Overall, reported flu and cold symptoms in the test group decreased by 85% compared with the control group after the administration of megadose Vitamin C.
Here's where it gets interesting for SARS viruses specifically (since it's not the flu!).
There is an interesting "drop" in interferon production early in the infection phase which doesn't generally happen with other viruses:
In a murine model of SARS infection, fast and robust virus replication accompanied by a delayed-type I IFN (interferon) response. Accordingly, type I IFN expression was barely detectable in most cell types.
Interferon is our body's primary defender against virus infections.
This delay in response and a rapidly expanding viral load sets the body up for a massive overreaction and resulting lung damage.
Where it gets deadly is when the lungs, heart, and other organs can't handle the sheer amount of oxidative damage.
This is generally called sepsis and it's what kills us.
There's a wide review of Vitamin C for sepsis here but a key takeaway specific to serious viral infections:
Experimental data in an animal sepsis model demonstrated that vitamin C diminishes pro-inflammatory and pro-coagulant changes that induce lung vascular injury.
The lungs...the site of the most acute damage with the SARS family of viruses.
Again, a laundry list of positive effects when the body is under assault here:
It isn't that vitamin C has some magical effect. It's more a case of a very basic building block for our damage control system (redox, detox) is depleted in a viral infection setting and restoring or buttressing those pathways is critical.
Vitamin C won't save you but depleting it might kill you.
Speaking of sepsis (basically, system failure).
CBD and Viral infections
Let's look at some highlights.
First, there's the antiviral aspect but from a different angle.
Where most of the supplements above gum up the system for viruses to make more of themselves (quercetin and PH balance, NAC and thiols, etc), CBD has a direct effect on the cell removal, death side.
Technically, the term is apoptosis.
It's how our body (immune system really) gets rid of faulty or infected cells.
This applies to cancer as well as virally infected cells.
It turns out this balancing system between cell birth and death is partially under the command of the endocannabinoid system where CBD works.
This system is tasked with homeostasis (fancy word for balance) for other major systems:
- Nervous system - neurotransmitters such as GABA, serotonin, and others
- Endocrine system - hormones including steroidal, metabolic, and stress-related
- Immune system - cytokines!
A quick look at cancer is a great primer for CBD's true ability.
- Healthy cell, low inflammation - CBD has no effect
- Healthy cell, high inflammation - CBD reduces inflammation
- Cancerous or pre-cancerous (or virally infected cell as we'll see) - CBD INCREASES inflammation!
Keep in mind that inflammation in the form of oxidative stress is how our body kills off wayward cells.
Afterall, chemo and radiation are just massive amounts of hopefully targeted oxidative stress.
Those are three different effects from CBD depending on the state of the cell!
Let's look at an example of this for viruses:
While CBD induced dose-dependent apoptosis in both cell types, at 0.25 to 1.0 µM, CBD induced significantly more cell death in the virus-infected HMVECs than in the mock-infected HMVECs.
This was a test on a specific herpes virus that causes cancer.
Interestingly, CBD caused cell death (apoptosis) in the infected cells but not the healthy cells.
Again, it worked from the backend:
While CBD did not affect the efficiency with which KSHV infected ECs, it reduced proliferation and induced apoptosis in those infected by the virus.
This is critical since an infected cell will continue to spew out more virus particles to infect other cells.
We also looked at CBD and the cytokine storm aspect...an overkill by our immune system.
CBD can also have different results depending on the state of the immune system.
This is in direct contrast to THC which is always suppressive. That's not a good place to be when under attack from a virus.
Again, it's all about balance.
Let's look at the extreme where a virus becomes lethal by causing so much immune response that our system shuts down.
Let's focus on the lungs since they're under direct assault with certain viral infections.
Researchers caused acute (serious) infection in the lungs of mice with some getting a pretreatment with CBD.
The result was across the board:
The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant.
The most important piece was the result….improved lung function.
If you look at the reports on the end stages of viral infection, it's a total loss of lung function as they fill up with cytokines (our immune agents) and fluid.
Eventually, ending in organ failure or sepsis.
Another study created the same situation in mice by puncturing intestinal tracks (science can be brutal).
The body rushes in with immune responders (similar to the lungs with viral infection) and the result is usually death.
Look at the effect of CBD:
The acute and extended administration of CBD at different doses reduced TBARS and carbonyl levels in some organs and had no effects in others, ameliorated cognitive impairment, and significantly reduced mortality in rats submitted to CLP.
The key words there "significantly reduced mortality".
Again, it wasn't the injury that killed the mice but the immune's inflammatory response.
Check out CBD as antiviral for other aspects as well.
Let's look at ginger.
Runner Ups for Antivirals
There's a list of different supplements that have some antiviral effects which we didn't go into full detail.
- Vitamin D
We didn't include these since they are generally safe but can have side effects or interactions with medications while the three above are more benign.
That being said, you still should work with a naturopath or doctor with any supplement.
For the runner-ups.
Elderberry and Viral infection
We covered its method of action in our CBD as antiviral article.
It appears to thwart viral reproduction early in the infection but there are questions on whether it's a good thing later in the process.
Ginger and Viral Infection
There are studies on Ginger and H1N1 flu viruses and cold viruses that we referenced in our antiviral article.
Ginger, long known for nausea, may reduce blood pressure and cause dizziness as a result.
There are also questions on thinning blood for those on similar medications.
Again, always work with a medical professional if you have health issues or medications.
Turmeric and Viral infection
Turmeric is generally safe and may have antiviral effects in terms of interfering with the virus binding to cells.
An early study showed that it reduced the activity of HIV by binding to the virus itself (so it's less able to bind to our cells):
The authors found that the molecule binds to multiple sites of the enzyme, with micromolar concentrations leading to a suppression of enzymatic activity.
Turmeric is generally safe to use but make sure to work with your doctor.
EGCG (green tea extract)
This molecule has the same effect on transporting zinc across the cell membrane to increase PH (which interferes with SARS virus replication) like quercetin above.
The two had comparable effects on this pathway (see Hydroxychloroquine versus quercetin for viral infections) but the safety profile for quercetin is much better.
You can drink green tea to get its benefits.
Garlic and Viral Infection
Remember how we discussed thiols above in that NAC interfered with viral function?
Thiols are what gives Garlic its strong smell.
If we drill down further, we can see the telltale signs.
Most research points to allicin as the key component in Garlic for antiviral effects.
What is allicin?
Hmmm….very similar to N-acetylcysteine (NAC) as a donor of cysteine (a thiol).
The issue is that garlic may be immunostimulatory (boost immune response and cytokine activity).
This can be tricky during later phases of viral infection progression such as with the cytokine storm.
Again, immunosuppressant or immune-boosting chemicals are tricky in such a complex system.
That's why we focus on supplements that directly impair the viruses' ability to thrive (Quercetin and NAC) or counter the damage from the immune response (CBD).
With strong safety profiles.
Like we promised in the title!
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.