Cannabis contains myriad chemicals called cannabinoids. And while the most famous are perhaps THC, tetrahydracannabidoil, and CBD, cannabidiol — maybe CBGA (cannabigerolic acid) and CBDA (cannabidiolic acid) should be on your radar, too. That’s if a preliminary, drug-screening study is to be believed: The now-viral study, published Monday in the Journal of Natural Products, suggests these two cannabinoids may block a critical stage of the infection of human cells by the SARS-CoV-2 virus, which causes Covid-19.
What’s new — Researchers from Oregon State University used a screening tool to search for chemical compounds with certain features that may make them useful drugs to treat or prevent a Covid-19 infection. They discovered two — CBGA and CBDA — with the right molecular make-up to suggest they could block the SARS-CoV-2 virus’ spike protein from binding to a cell and unlocking it, thereby infecting the cell and turning it into a viral factory.
They then tested the compounds in human cells in a petri dish — these cells are called epithelial cells, and they are essentially the cells that line the walls of bodily tissues, like the lungs. In the cell models, both compounds appeared to hamper the ability of the spike protein to bind to the epithelial cells in much the same way as monoclonal antibodies, a known treatment for Covid-19 infections. This was true for both the alpha and beta variants of the coronavirus. The researchers did not test any other variants.
Importantly, this study is not evidence that smoking weed or consuming hemp-derived products like CBD gummies can protect or prevent a Covid-19 infection.
“CBDA and CBGA are produced by the hemp plant as precursors to CBD and CBG, which are familiar to many consumers. However, they are different from the acids and are not contained in hemp products,” lead researcher Richard van Breemen says in a statement. Van Breemen is a pharmacologist and professor at the Linus Pauling Institute at Oregon State University.
Why it matters — These kinds of drug screenings are used all the time — the idea is to look at drugs or chemicals we already know about and see if any have essential features that might make them good weapons against a virus’ mechanisms, or a disease’s progress. By searching through the annals of what we know rather than attempting to discover or invent something that we don’t, scientists may be able to find and develop drugs to fight infections more quickly than starting from scratch because they have already been tested for safety and human use to some degree.
“These compounds can be taken orally and have a long history of safe use in humans,” van Breemen says. “They have the potential to prevent as well as treat infection by SARS-CoV-2.”
How it works — The reason why CBDA and CBGA may be promising drug targets is that both appear to prevent the SARS-CoV-2 spike protein from binding to a receptor on the outer layer of cells, called ACE2.
When the spike protein binds to ACE2, it’s akin to turning a key in a lock — it opens the cell up to the virus and the virus gets to work inside, turning the cell into a viral factory and establishing a Covid-19 infection. Interfering with this mechanism is critical to preventing and treating Covid-19 — one could ostensibly stop cells from becoming infected, but one could also curtail an infection by limiting its reach on the body’s cells.
The researchers identified the two cannabinoid compounds by looking for ligands among these compounds — molecules that might bind to the SARS-CoV-2 spike protein as the ACE2 receptor does.
“The two cannabinoids with the highest affinities for the spike protein were CBDA and CGBA, and they were confirmed to block infection,” van Breemen says in the statement.
An important caveat to note when considering this study is that the work is preliminary — cell models and screens are not a substitute for human clinical trials, the gold standard in drug development. We are a long, long way from utilizing these findings to treat Covid-19 in a clinic. Importantly, we still don’t know how well the compounds work at curtailing an infection, or how much of the compounds are needed to play a therapeutic role.
What’s next — This study is preliminary and needs to be validated with further work. But already it has garnered a huge amount of interest from the public. According to the journal’s metrics tracking, which tracks mentions of the study on the internet, at the time of writing some 14 million people have seen the study via Twitter alone.
In the meantime, back in the lab van Breemen is concerned with expanding the work to see how CBDA and CBGA might fare against other Covid-19 variants.
“Our data show CBDA and CBGA are effective against the two variants we looked at, and we hope that trend will extend to other existing and future variants,” he says.
He also hopes to test a different plant-derived chemical, this time from licorice, as a potential drug target for SARS-CoV-2.
“Our earlier research reported on the discovery of another compound, one from licorice, that binds to the spike protein too. However, we did not test that compound, licochalcone A, for activity against the live virus yet. We need new funding for that,” he says in the statement.
Abstract: As a complement to vaccines, small-molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants, which cause COVID-19. Affinity selection-mass spectrometry was used for the discovery of botanical ligands to the SARS-CoV-2 spike protein. Cannabinoid acids from hemp (Cannabis sativa) were found to be allosteric as well as orthosteric ligands with micromolar affinity for the spike protein. In follow-up virus neutralization assays, cannabigerolic acid and cannabidiolic acid prevented infection of human epithelial cells by a pseudovirus expressing the SARS-CoV-2 spike protein and prevented entry of live SARS-CoV-2 into cells. Importantly, cannabigerolic acid and cannabidiolic acid were equally effective against the SARS-CoV-2 alpha variant B.1.1.7 and the beta variant B.1.351. Orally bioavailable and with a long history of safe human use, these cannabinoids, isolated or in hemp extracts, have the potential to prevent as well as treat infection by SARS-CoV-2.