Is Baicalein From Skullcap Effective Against COVID-19?

A new preprint* released yesterday suggests that ethanol extracts of Scutellaria baicalensis (Chinese Skullcap), or the specific compound found within it known as baicalein, may be effective against COVID-19. However, the way in which baiclaein is metabolized in humans raises some questions that make this herb, in my judgment, unready for prime time.

Please note that I am not a medical doctor and this is not medical advice. I have included a more detailed disclaimer at the bottom. Please note also that neither baicalein nor skullcap have been tested in clinical trials to show they are safe and effective in the specific context of COVID-19.

Chinese Skullcap and the Baicalein Within It Inhibit the Replication of SARS-CoV-2

A crude ethanol extract of Chinese Skullcap inhibited the 3CL protease, also known as the “main protease,” of SARS-CoV-2, the coronavirus that causes COVID-19. The 3CL protease is a key enzyme required for viral replication. It also inhibited the ability of the virus to replicate in vero cells, which are cells used for experiments that are descended from cells taken from African green moneys.

The most effective compound within the extract was baicalein.

A standard metric used to see how much of a particular compound is needed to inhibit an enzyme or the replication of a virus is the concentration required to inhibit either one by 50%, measured as an IC50 or EC50 (IC is for inhibitory concentration, while EC is for effective concentration).

For inhibition of the enzyme, the crude extract had an IC50 of 8.5 micrograms per milliliter (ug/mL), while baicalein had an IC50 of 0.39 micromoles per liter (uM), which is equilvant to 0.01 ug/mL. That makes isolated baicalein about 800 times more powerful than the crude extract.

For inhibition of viral replication, the crude extract had an EC50 of 0.75 ug/mL, while isolated baicalein had an EC50 of 17.6 uM, the equivalent of 0.48 ug/mL. Baicalein is thus only about 1.5 times more powerful than the crude extract when it comes to inhibiting the replication of the virus.

The fact that baicalein was 800 times more effective at inhibiting the main protease but only 1.5 times more effective at inhibiting viral replication suggests that there are other compounds within the extract that have other targets besides the main protease that are useful in inhibiting viral replication.

The isolated baicalein is still a little more powerful than the crude extract, but an extract standardized to provide at least the necessary antiviral dose of baicalein, plus the other unknown components, might be more effective than the dose of baicalein alone, and might be more robust to unforeseen problems since it isn't relying on a single mechanism.

What Dose Would We Need?

How much would we need to consume to have these effects?

Unfortunately, most baicalein is rather quickly metabolized within the human body to baicalin (spelled the same but without the “e”), which has a sugar attached to it. One study found that an 800 milligram (mg) dose of baicalein gave rise to plasma concentrations of 0.029 ug/mL baicalein within 4 hours, while it gave rise to a much higher plasma concentration of 0.396 ug/mL baicalin by 3.5 hours.

Unfortunately the concentrations of baicalein reached are 16 times lower than those needed to slow SARS-CoV-2 growth down by 50% in a test tube.

The only way a safety-tested dose of baicalin could work under these circumstances is if its sugar-bound metabolite is just as effective as it is.

When dosing something continuously, a dose taken every half life will eventually result in a more or less constant concentration in the blood that is roughly double the concentration achieved with a single dose.

The study that looked at the 800 mg dose also looked at 400 mg. 400 mg baicalein led to maximal plasma concentrations of 0.275 ug/mL baicalein within 1 hour, with a halflife of 12 hours. This suggests that 400 mg baicalein taken twice a day 12 hours apart would lead to a roughly steady concentration in the blood of 0.55 ug/mL, which exceeds the concentration required to inhibit half the viral growth in a test tube.

Unfortunately, baicalin might not be anywhere near as effective at inhibiting viral growth as baicalein.

Is Baicalin Less Effective Than Baicalein?

This weekend's preprint unfortunately only compared the ability of baicalein and baicalin to inhibit the main protease enzyme and didn't compare their ability to inhibit viral replication.

Baicalin required more than 128 times the concentration of baicalein to inhibit half the enzyme's activity.

It strikes me as a major oversight of the researchers to not also test baicalin's ability to inhibit viral replication. Their results with the crude extract showed that it contained compounds that clearly had other targets than the main protease. The superiority of the baicalein over the crude extract was 800-fold for the enzyme and only 1.5-fold for inhibiting viral replication. Its superiority over baicalin for the enzyme was only 128-fold, so it is certainly possible that it is only slightly superior or not even superior to baicalin for inhibiting viral replication.

The Verdict

I will be keeping my eye on Chinese Skullcap and baicalein as possible additions to my personal regimen as well as my protocol in The Food and Supplement Guide for the Coronavirus, but I will not be adding them at this time.

My suspicion is that this will only be useful if baicalin turns out to be just as antiviral as baicalein. The results of this weekend's preprint do not support that conclusion, but I hope the authors test it more carefully in the near future by testing the direct ability of baicalin, the sugar-bound metabolite, to inhibit viral replication.

Stay safe,

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I am not a medical doctor and this is not medical advice. I have a PhD in Nutritional Sciences and my expertise is in conducting and interpreting research related to my field. Please consult your physician before doing anything for prevention or treatment of COVID-19, and please seek the help of a physician immediately if you believe you may have COVID-19.


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*  The term “preprint” is often used in these updates. Preprints are studies destined for peer-reviewed journals that have yet to be peer-reviewed. Because COVID-19 is such a rapidly evolving disease and peer-review takes so long, most of the information circulating about the disease comes from preprints.