Since the onset of the COVID-19 Pandemic in recent years, the novel coronavirus SARS-CoV-2 has left a lasting mark on our world and our lives, reshaping the entirety of society in unprecedented ways, the most visible of which remains its impacts on the lives (and deaths) of more than 5 million people worldwide, going on the number of cases recorded.
Scientists and Healthcare have spent unceasing moments attempting to configure an understanding and deconstruction of this virus in an effort to develop vaccines and limit the destructive impact of this illness. This has further been complicated by the rise of the many emerging variants of SARS-CoV-2, which complicate the existent understanding of COVID strains and limit the efficacy of existing methods to combat them.
However, via consistent and continuing research into the subject, the various avenues explored to develop therapies and treatments for this virus have paved the path toward the discovery of the impact of Cannabinoids in aiding the blockage of cellular entry of SARS-CoV-2 and its multitude of variants Cannabinoids, compounds found in Cannabis plants, are renowned to various extents for their therapeutic properties, and that is translating to the impact of this compound on the COVID virus’ spike protein.
This leads us to this article, which attempts to explore the very complexities and consequences that the role and potential impact of Cannabinoids on SARS-CoV-2 has on the future of COVID-19 and its emerging variants.
Understanding SARS-CoV-2 and Its Spike Protein
SARS-CoV-2 is a member of the already-existent Coronaviridae family and functions as an RNA virus. It is an enveloped, non-segmented, and positive sense virus with RNA strands that are 29.9 kb long. It is further depicted and known to have spikes on the outer layer (surface) of the virus, which are crown-like in characterization.
The RNA strands, in turn, are incumbent in encoding various proteins:
- Spike, a main structural protein
- Envelope, a main structural protein
- Membrane, a main structural protein
- Nucleocapsid, a main structural protein
- 16 nonstructural proteins
- Accessory proteins
Of these, the spike protein is the most essential in the infection of human cells, insomuch that it is critical that the viral spike protein is able to securely bind to the human cell surface receptor angiotensin converting enzyme-2 (ACE2).
More specifically, the spike protein is a transmembrane protein that forms homotrimers (proteins composed of three identical polypeptide units), which protrude from the surface of the SARS-CoV-2. Subunits of these trimers allow the entire unit to be bound to the ACE2 of the host cells, which allows the infection to spread. Yet another subunit allows for the virus to fuse with the host cell, making it even easier for the virus to take hold. With the activation of the spike protein, the fusion completes, and the virus-cell enters the cytoplasm.
With that in mind, logic dictates that cell entry inhibitors would be essential in preventing viral proteins and particles from entering human cells in the first place, which in turn would both be liable to prevent the SARS-CoV-2 infection and limit the length of the virus should someone be infected.
The Emergence of New Variants
It is not news that the coronavirus has branched into multiple variants as the human body grows resistant to the original strain. Because of that, the second phase of the COVID-19 Pandemic was so terrifying for everyone involved.
These variants are created by changes in the genetic coding of the virus, even something as small as an amino acid exchange, because SARS-CoV-2, quite similar to other RNA viruses, is susceptible to genetic evolution. These mutations then affect the various characteristics of the virus, including but not limited to the transmissibility, virulence, and efficacy of vaccines and treatments in response to the virus itself.
These variants are many in number and are monitored constantly based on their designations of VOC, VOI, and so on, but a few of these are significant enough to be named, and they are as follows:
- Alpha
- Beta
- Gamma
- Delta
- Omicron
These variants, purely on the basis of existence, have changed the landscape of virus prevention, introducing new variables that may, in turn, be resistant to the vaccines produced. This is where the importance of Cannabinoids shines through, with their characteristic blockage of cellular entry.
Cannabinoids: A New Avenue for COVID-19 Therapeutics
Cannabinoids are a diverse group of compounds found in cannabis, with over 100 identified to date. In classic research and literature, of these numerous compounds, two, specifically, are well-known: cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC).
CBD, in particular, has garnered interest for its reported anti-inflammatory and immunomodulatory properties, which refers to the healing and therapeutic properties of Cannabinoids in general, leading to a greater avenue for exploration specific to the SARS-CoV-2.
How Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants
To work with and counter the spike protein entry into host cells, research into ligands and cellular entry inhibition using Cannabinoids was conducted. Ligands, as molecules that attach to a metal atom by bonding, would allow medical professionals to initiate a process that bonded these Ligands to bond with the spike protein subunits.
Ligands
The study thus conducted research into Ligands in an attempt to discover which specific molecules would take that position specifically with SARS-CoV-2 spike proteins. This is because Ligands with high affinity to bind to those proteins would function as entry inhibitors since they would bind the protein subunits and stop them from breaching the cell wall, minimizing the chances of the virus’ fusion with the cell.
Furthermore, the reason that natural ligands were used in an attempt to discover which held the best affinity for attachment was because of the history of natural products being utilized as the best drugs and therapeutic substances for patients and the overall industry of pharmacology.
The Process of Discovery – The Research
Affinity Selection-Mass Spectrometry (AS-MS) was chosen as the method for Ligand selection for this study because AS-MS allows the incubation of the receptor (in this case, the spike protein, i.e., SARS-CoV-2) with a mixture of possible Ligands.
The Ligand-Receptor mixture was then separated from any non-binding molecule using magnetic microbeads. With the utilization of magnetic microbead affinity selection screening (MagMASS), it was discovered that the highest affinity for receptor-binding was ligands from hemp extracts.
Hemp – Cannabinoids and Compounds
Hemp, in general, refers to a botanical class of Cannabis sativa cultivars, and it is, in modern times, grown specifically for industrial and medical uses. It is used for fiber, food, health products, fabric, rope, natural remedies, and much more.
On a more industrial basis, the compounds from Hemp are also used in cosmetics, lotions, and dietary supplements. This makes the idea of using these compounds as ligands for SARS-CoV-2 a potentially good idea, especially since certain compounds from Hemp are also FDA-approved for the treatment of a limited type of seizures, making it relevant to medical history.
Regardless, in connection to the study, Hemp Cannabinoid Ligands were shown to have high affinity to the SARS-CoV-2 spike protein, especially cannabidiolic acid (CBDA), tetrahydrocannabinolic acid (THCA-A), and cannabigerolic acid (CBGA), showing results by blocking infection of human epithelial cells by a pseudovirus expressing the spike protein, and in blocking infection of the original COVID virus and variants. Other cannabinoid ligands showed only weak responses to the affinity selection and were discarded.
The Results of the Research
The results in relation to both the pseudovirus and the live SARS-CoV-2 virus were conducted to confirm initial screening and safety while further allowing for real-life applicability in terms of efficacy of the natural product (Cannabinoids) in blocking the cellular entry of SARS-CoV-2 and its variants.
When the incubation of the live SARS-CoV-2 cells was carried out alongside the application of the Cannabinoids, the study also quantified the level of inhibition using fluorescence microscopy. The results of the tests showed that CBDA and CBGA were clearly able to inhibit the infection of host cells by the original coronavirus strain as well as other mutated strains for assessment of applicability to emerging variants.
The study does inform that the concentration of cannabinoids used to inhibit 50% of viruses is admittedly high but theoretically clinically acceptable for patients. However, the fact that the variation in COVID virus strains – which lowers the efficacy of vaccines and boosters depending on the resistance of the new strain to older vaccines and other such implications – does not impact the effects of CBDA and CBGA (according to existing research, that is) makes it a particularly revolutionary response to the COVID-19 pandemic.
Results – Variants and Future Possibilities
Nevertheless, despite this hopeful note, widespread use of cannabinoids may indeed lead to resistant strains that are able to resist the binding with the spike proteins or escape the trap laid out by the Ligands.
However, we cannot control that future possibility and must rely on the fact that the situation created by the ligand-receptor binding will help slow the virus down. This is especially true if research continues on this idea and attempts to discover possible cannabinoid compounds, ligands, or combinations that work more effectively to inhibit the entry of SARS-CoV-2 and its emerging variants into host cells.
Implications for Vaccines and Boosters
The research outlined and theorized above (in terms of future applicability and improvement) about Cannabinoids and their ability to block cellular entry of SARS-CoV-2 and its variants is a hopeful way of looking at the future, especially if seen in conjunction with (rather than as a replacement of) COVID-19 vaccines and boosters.
In fact, Cannabinoids can serve as an added treatment, aiding in minimizing the effects or limiting the possibility of infection, working much like boosters do in the way of aiding the immune system in immediately inhibiting the entry of the coronavirus.
So, in that regard, it is important to understand the essential nature of vaccines as a primary defense mechanism, which an individual cannot disregard in favor of cannabis and its compounds. Instead, as new variants emerge and vaccine efficacy potentially decreases, Cannabinoids can be taken as supplementary therapeutics, much as Cannabis and Hemp have been used for other illnesses.
However, that is not to say Cannabinoids will have no impact if not paired with vaccines and boosters. Rather, both treatments have their own benefits. For example, in the case of excessively immunocompromised individuals who are not affected by vaccines, either due to exposure or the change in variants, Cannabinoid-based therapies would be significantly helpful in reigning in the potential devastation of the SARS-CoV-2 infection.
Indeed, the integration of cannabinoids into COVID-19 vaccination strategies is a truly ingenious conceptualization and one that demands further research, especially if that research is liable to discover ligands or compound combinations that are more effective in reigning in the coronavirus infection. The rigorous scientific investigation will thus be essential in validating their efficacy, establishing safe dosages, and determining any potential interactions with existing treatments.
Conclusion
In the relentless battle against COVID-19 and its constantly evolving variants, the discovery of cannabinoids as potential viral entry inhibitors offers a ray of hope for the future. From the initial screening to the confirmation of efficacy against both the SARS-CoV-2, this research has unveiled an approach to combating the virus’s cellular invasion that may, indeed, end up revolutionizing preventative measures.
Cannabinoids, particularly CBDA and CBGA, have shown remarkable affinity for the spike protein of SARS-CoV-2. As demonstrated in the research, their ability to bind and thereby block viral entry into host cells presents a promising therapeutic avenue.
While challenges lie ahead, including the need for further research and clinical trials, the fact that cannabinoids have maintained their efficacy against the virus’s variants is a significant breakthrough.
As we stand at the intersection of science and medical innovation, the journey to harness the full potential of cannabinoids in the fight against viral pandemics is just beginning. With dedication, collaboration, and continued research, we may find ourselves equipped with a potent tool to combat the pandemic and its emerging variants, ultimately paving the way for a safer and healthier future for all.
