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Did you hear? CBDA and CBGA have been shown to prevent SARS-CoV-2 from infecting human cells–what does this mean to you and me?

Just last week this research made the rounds within all the social media outlets.  Were you curious about this research and what it actually means?  I’ve decided that this research would be a great first blog for Natural Kore Laboratories! The research article “Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants”1 by van Breemen and collaborators was published initially online in the Journal of Natural Products.  These interesting research studies demonstrated that cannabinoid acids like CBDA and CBGA could prevent or reduce SARS-CoV-2 infection. Let’s dig deeper into these studies. What are the actual findings and how is it related to us in the world of escalating SARS-CoV-2 infections and COVID-19 cases? 

Research summary 

Let’s first quickly summarize the research findings by van Breemen and collaborators:2 

  1. They demonstrated that cannabinoid acids (specifically, THCA, CBDA, and CBGA as seen in Figure 1) strongly interacted with the virus’ spike protein found on the surface of the SARS-CoV-2 virus (See Figure 2 which highlights the virus structure). Other cannabinoids including the decarboxylated versions, Δ9-THC, CBG, CBD, as well as Δ8-THC, and CBC, either didn’t bind/interact, or did so, but poorly. 
  1. Next, they calculated how well CBDA, CBGA and THCA interacted with the spike protein.  CBDA interacted slightly better than CBGA and THCA.   
  1. By doing computer modeling studies, they calculated the 3-D shape and how well CBDA, CBGA and THCA interacted with the spike protein at the atomic level. They also demonstrated that CBGA, CBDA and THCA interacted with the spike protein of two virus variants (alpha and beta). 
  1. Then, they showed that CBGA and CBDA prevented the SARS-CoV-2 virus from binding to and infecting human cells grown in a petri dish. See Figure 4 for more details.   
  1. Finally, they did several control studies to make sure their observations were accurate.   

Figure 1: A small section of cannabinoid biosynthetic pathway in plants.  CBGA (cannabigerolic acid) is the parent molecule that can be converted in the plant to either THCA (tetrahydrocannabinolic acid) or CBDA (cannabidiolic acid) by independent pathways.  THCA is then decarboxylated to Δ9-THC (Δ9-Tetrahydrocannabinol).  CBDA is also decarboxylated to CBD (cannabidiol).  The decarboxylation method is a natural process, not driven by the plant metabolism (we call this “uncatalyzed”). Decarboxylation is a very slow process in the absence of heat.   

What does this all mean?  

First, let’s define important properties of viruses and host cells.  Viruses have very specific proteins that are found on their surface.  The SARS-CoV-2 has its own type of proteins, and these surface proteins differ from, for example, the influenza virus surface proteins (you might be familiar with the terms like “H1N1” variants for the flu.)  SARS-CoV-2 has a protein called the spike protein, and it’s shaped like, well, a spike (See Figure 2)!  In a similar fashion, cells have proteins on their surface as well.  Some of these proteins are called receptors. These surface proteins will differ depending upon the cell type (lung cell, white blood cell, liver cell, etc.).  Lung cells, and a few other types of human cells, have a receptor named the ACE2 receptor (see Figure 4, blue rod). The spike protein and the ACE2 receptor have an affinity for each other (more on this in a minute). 

Figure 2: General structure of the SARS-CoV-2 virus.3


Now that the virus and cell terminologies have been defined, I’ll use an analogy to outline how viruses infect the host cell.  Let’s consider a helicopter and an “X” landing pad on the top of a large hospital.  The normal process is to land the helicopter exactly onto the X, knowing that it can’t land anywhere else (Figure 3A).  Expand this scenario and identify the helicopter as the virus, and the X landing pad on the building is the receptor on the human cell. Therefore, the virus (helicopter) identifies a recognizable receptor site on the human cell surface (the X), interacts with that receptor (it lands), and then infects the human cell (passengers exit the helicopter and enter the hospital).  Here, the X landing pad is very specific to that helicopter.  Likewise, as mentioned above, viruses have very specific surface proteins that interact with very specific cell receptors. The SARS-CoV-2 surface spike protein only likes to land on cells that have the ACE2 protein receptor on its surface. Only a few types of human cells have this ACE2 protein receptor on its surface, certain lung cells are the primary pathway for SARS-CoV-2 infection. 

Figure 3:  Helicopter and X landing pad analogy. 

Let’s go back to our helicopter/X landing pad analogy.  Now imagine that someone parked their bicycle in the middle of the X landing pad on top of the hospital (Figure 3B).  The helicopter can no longer land on that landing pad.  In this case, the CBDA molecule (the bicycle) is interacting with the virus spike protein (helicopter) that is trying to identify and bind to the specific ACE2 receptor (X landing pad).  It won’t be able to interact/bind (land) and will be unable to infect the cell (unload its passengers). The CBDA molecule is in the way (the bicycle is blocking the X landing pad). Figure 4A and B takes the analogy from Figure 3 and applies it to a virus and host cell. For clarity, Figure 4C and D zoom into the virus spike protein and the ACE2 receptor.  The net result is when CBDA, CBGA or THCA was present in the petri dish when the host cell was introduced to the SARS-CoV-2 virus, the virus couldn’t land.  If the virus can’t land on the cell, it can’t infect/invade the cell.  Also, if it can’t infect the host cell, it can’t replicate either.2

Figure 4:  Pathway for a virus to infect host cell.  A.  Unimpeded virus with the spike protein on its surface interacts with the ACE2 receptor (blue rod) on the host cell surface.  The virus now can invade/infect the cell.  B.  With CBGA added to the host cell petri dish, CBGA interacts with the spike protein on the virus surface, blocking the virus’ interaction with ACE2 receptor on the human host cell. C. Spike protein and the ACE2 receptor.  D. CBGA blocking the interaction between the spike protein and ACE2.  These structures are not drawn to scale. 

What does this mean to you? The big questions! 

It should be emphasized that this research is based on “in vitro” studies – meaning, the researchers used specific and controlled research environments so they can determine whether the virus, SARS-CoV-2, is prevented from infecting human cells.  This research study was not conducted on humans, rather, on human cells growing in a petri dish.  

We now need to consider how this can be applied to us.  First, it’s evident that the acid version of cannabinoids is important (CBDA, not CBD).  Most CBD products have been “decarboxylated.” Even most of our Natural Kore products are decarboxylated so that the CBD, CBG are in the “active, decarboxylated state.” Next, dosage at the petri dish level might not easily translate to an oral dosage in humans. Third, let’s consider 200 mg ibuprofen, a known pharmaceutical. A typical dose is 200 mg ibuprofen for a backache. Not all the oral dose is available to do its “job” targeting the backache.  The ibuprofen goes everywhere, not just to your back.  In addition, you will need to take a second dose every 4-6 hours, because the body has a way of breaking it down and removing it from being available (“bioavailable”). Thus, we need to consider how much and how often.  Finally, because SARS-CoV-2 targets lung cells, you might consider inhaling Cannabis flower so that it goes directly to the lungs.  Unfortunately, that requires heat (vaping or smoking), and heat accelerates the decarboxylation of the cannabinoid acids, thus you lose the beneficial CBDA, CBGA and THCA (revisit Figure 1 for more details).2  Because there are no guidelines right now, I will not speculate what the best delivery method or dosage may be.  Always consult your health care provider for their advice.   

For now, the research is promising, but how it applies to a ‘prophylactic dose’ of CBDA or CBGA to prevent SARS-CoV-2 infection is presently unknown! 

1. van Breemen, R.B., Muchiri, R.N., Bates, T.A., Weinstein, J.B., Leier, H.C., Farley, S. and Tafesse, F.G.. Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants. J. Nat. Prod. 2022, 85 (1), 176-184. DOI: 10.1021/acs.jnatprod.1c00946 https://pubs.acs.org/doi/full/10.1021/acs.jnatprod.1c00946

2. Simplified for discussion purposes.

3. Coronavirus Photo by CDC from Pexels

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