Zach

Could Resveratrol protect against SARS-CoV-2?

A couple of weeks ago I came across some interesting research about Resveratrol. If you’re unsure what that is, I would recommend reading this page. A study was published in 2017 titled; Effective inhibition of MERS-CoV infection by resveratrol. MERS-CoV is a coronavirus, while it’s distinct from SARS coronavirus, it is in the same group. The study tests the possibility that Resveratrol could inhibit MERS-CoV from infecting cells. It was found to be useful and the conclusion of the study was that it could be a potential anti-MERS agent. This raises the question, could Resveratrol protect against SARS-CoV-2? In other words, the virus responsible for the current pandemic, COVID-19.

Can it fight SARS-CoV-2?

There’s not quite enough evidence to deem it beneficial in defeating MERS-CoV. Unfortunately, there is also no evidence for it working against coronaviruses in-vivo (humans & animals). The study was done in-vitro (tested on cells), which doesn’t exactly simulate a human or animal body. Resveratrol is thought to be beneficial for cellular health, although strong evidence is lacking. On the other hand, many of the studies done on it point out that it’s poorly bio-available. Resveratrol may be promising if bio-availability can be increased, as many in-vitro studies have shown it to be promising. Studies in mice also seem to be promising for treatment and prevention of several diseases. Don’t believe me? Take a look!

That begs the question, can it fight SARS-CoV-2? The answer is, maybe. If it can inhibit and prevent the infection of MERS-CoV in humans as it does in cells, it’s possible it can do the same against SARS-CoV-2 and prevent COVID-19.

Chemical structure of trans-resveratrol, the most active of Resveratrol.

Is it worth trying?

I think it is, if the bio-availability can be improved it could have a lot more potential. There needs to be more research done in humans as well (which is ongoing). I believe the failure of Resveratrol as a promising supplement or medication came from the failure of a company, Sirtuis Pharmaceuticals. Not only that, it is poorly bio-available in its standard form. It has received a bit of stigmatism as well, because of overly hopeful remarks made by some researchers. Overall, I believe it still has promise. It’s widely available for purchase and sometimes bundled with Quercetin and Nicotinamide Riboside. Just make sure you research the brand before trying.

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Drug-drug interactions, be cautious when combining medications

When taking supplements and or medication, extra precaution should be taken. Not only can there be neurological interactions, there can also be drug-drug interactions with how fast or slowly a supplement or drug gets metabolized. These factors can determine whether a drug can buildup too much or not well enough. Always check with your doctor before starting a supplement if you are taking a prescribed medication. That statement is cliche, but very important!

Drug Metabolism

The Cytochrome P450 system is responsible for metabolizing 75% of drugs. Without getting too in-depth, Cytochromes P450, commonly abbreviated as CYP are a family of enzymes. They are encoded with a gene family, for example one of the most common ones is 2D6 (making it CYP2D6). These enzymes and their expression by our genes can be very important in how effective a drug is. To simplify it a bit and give an example, the over-expression of the CYP2D6 gene would cause one to be a rapid metabolizer of drugs that are broken down by the CYP2D6 enzyme. This could cause a drug to exit the body too quickly and be less effective. On the other hand, under-expression of CYP2D6 would cause someone to be a slow metabolizer of drugs broken down by that enzyme.

A good overview of the Cytochrome P450 system

Substrates, Inhibitors and Inducers

When taking different medications or supplements together, it’s important to examine how drug-drug interactions can occur. The most utilized CYP enzymes have a list of known substrates, inhibitors and inducers. With the CYP system, these 4 points are essential to understanding its role in the metabolism of drugs.

  • A substrate is a drug that a CYP enzyme breaks down and is crucial in its bioactivation.
  • An inhibitor prevents a substrate from binding to a CYP enzyme, inhibiting the substrate from being broken down by the enzyme.
  • An inducer increases the binding of a substrate to a CYP enzyme, causing it to be metabolized faster by the enzyme.
  • And interaction between a substrate and an inhibitor or inducer is called a drug-drug interaction.
CYP2D6’s structure, springs and spaghetti

Drug-drug interactions

Inhibitors

If 2 substrates (drugs) are taken together that are broken down by the same CYP enzymes, they may interact with each other in negative ways. For example, 2 substrates (A & B) will compete for a CYP enzyme and the strongest inhibitor, A will bind to the enzyme causing B to become inhibited by A. This inhibition would cause B to stay in the system longer as A is inhibiting the enzyme from binding to the B substrate. As a result, it can increase the potential for toxicity due to the drug’s buildup in the body. This could be dangerous as it could cause too much of a drug to be present, and for too long.

A real world example of a drug-drug interaction involving an inhibitor would be that of Cannabidiol (inhibitor) and Fluoxetine (substrate). Fluoxetine (Prozac), a common antidepressant is broken down by the CYP2D6 enzyme. Cannabidiol (CBD) is a strong inhibitor of the CYP2D6 enzyme, thus would inhibit Fluoxetine from binding with the CYP2D6 enzyme. This could cause a buildup of Fluoxetine in the body and cause more negative side effects, especially at large doses.

Inducers

In another example, taking 2 substrates, one as a substrate and the other as an inducer could make the substrate less effective. An inducer could cause the substrate to exit the system too fast. This would be cause for concern it would prevent a drug from working as intended.

An example of a real world inducer at work, causing drug-drug interactions, would be that of Phenytoin (inducer) and Ciclosporin (substrate). Ciclosporin is an Immunosuppressive drug that has several medical uses. Phenytoin is an anti-seizure medication used to prevent, you couldn’t have guessed, seizures. Phenytoin is a strong inducer of the common CYP3A4 enzyme. CYP3A4 is essential in the metabolism of Ciclosporin, thus with Phenytoin taken at the same time it interacts negatively. Ciclosporin’s metabolism would be sped up and it would become less effective. In other words, not lasting as long.

Genetics

With the CYP system, genetics are one of the key factors in drug metabolism. Those with certain genes may be over-expressed or under-expressed as discussed early on. Genetic testing can help determine which medication may work best for you. It can also determine which medication may give you more or less negative side effects as a result.

Conclusion

In conclusion, it is quite important to check for drug-drug interactions and you should always take precautions before starting a new medication or supplement. Your doctor would be the best choice if you’re not sure where to look. Data is less available on dietary supplements, which is unfortunate, so they may not know. If data is hard to find, try searching PubMed with the medication or supplement’s name including the abbreviation “CYP.” Google or other search engines are also your friends. Stay safe!

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References not linked in article

https://www.ncbi.nlm.nih.gov/pubmed/26651971
https://www.ncbi.nlm.nih.gov/pubmed/21821735
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1312247/
https://www.projectcbd.org/medicine/cbd-drug-interactions/p450