Dr. Richard van Breemen from the Department of Pharmaceutical Sciences in the Oregon State University College of Pharmacy discusses his COVID-19 and cannabis research.
Dr. Richard van Breemen from the Department of Pharmaceutical Sciences in the Oregon State University College of Pharmacy is an expert in biomedical mass spectrometry with a focus on natural products. He researches the discovery of drugs from botanicals and investigates the safety and efficacy of botanical dietary supplements. He has been named one of the top 100 analytical scientists from around the world.
Dr. van Breemen and a team of collaborators made headline news recently showing that specific hemp compounds demonstrated the ability to prevent the virus that causes COVID-19 from entering human cells. Findings of this groundbreaking study were published in the Journal of Natural Products. I sat down with Dr. van Breemen to discuss this study as well as future research.
Can you please tell Cannabis Science and Technology® readers how, when, and why the Oregon State’s Global Hemp Innovation Center was conceived? What is the mission of this center?
Industrial hemp has a long history in Oregon. Oregon State University (OSU) hosted a national hemp research center from the 1880s until 1936. With the passage of the 2018 Farm Bill, the Global Hemp Innovation Center at Oregon State was initiated and officially launched in January 2020. The mission of the center is to provide expertise and leadership to enhance hemp production and post-harvest industries.
You found that a pair of cannabinoid acids (cannabigerolic acid [CBGA] and cannabidiolic acid [CBDA]) bind to the SARS-CoV-2 spike protein, preventing entry into cells. Why did you begin to focus on COVID-19, and what were the major challenges early in this study?
In response to the COVID-19 pandemic during 2020, Oregon State University converted its classes to remote learning and curtailed most in person laboratory research. Those laboratories carrying out essential research, such as COVID research like ours, could remain open providing measures were put in place such as masking and social distancing. The major early challenges were funding and reduced staffing that was mandated by social distancing.
Can you tell us more about how this study was conceived?
For many years, the research in my laboratory has addressed the discovery of natural product therapeutic agents and the safety and efficacy of botanical dietary supplements. Including hemp natural products in our studies became possible only since the launching of the Global Hemp Innovation Center. The first step during infection of human cells by SARS-CoV-2 is binding of the viral spike protein to the human cell surface protein called angiotensin converting enzyme-2 (ACE2). Antibodies, which are large proteins produced by the immune system to combat viruses, neutralize SARS-CoV-2 by binding to the spike protein. We hypothesized that small molecule ligands from botanicals like hemp, if bound to the right location of the spike protein and with sufficient affinity, could also inhibit cell entry of SARS-CoV-2 and prevent infection.
The chemical screening technique used in this study was invented at OSU. Can you tell us a little about this technology, how it was developed, and what benefits it has compared to other screening approaches?
Central to our research has been the application of mass spectrometry and especially affinity selection-mass spectrometry (AS-MS). Mass spectrometers are analytical chemistry instruments that weigh molecules and are unsurpassed in their combination of sensitivity, selectivity, and speed. In this COVID-19 research, we applied the AS-MS methods we had pioneered called pulsed ultrafiltration (PUF) AS-MS and magnetic microbead affinity selection screening (MagMASS). AS-MS is ideal for the discovery of small molecules, such as those in botanical extracts, that bind to drug targets like the spike protein of SARS-CoV-2. In contrast, most pharmaceutical companies test individual compounds in drug discovery assays and hardly ever consider natural products or complex mixtures such as botanical extracts. We published our AS-MS assay for ligands to the SARS-CoV-2 spike protein in the Journal of the American Society for Mass Spectrometry at the end of 2021.
Were you surprised to see such strong binding by two specific cannabinoids (CBDA and CBGA)?
Hemp is an understudied and rich source of botanical secondary metabolites like cannabinoids, many of which are unique to this plant. CBD has already been approved by the US Food and Drug Administration (FDA) as an anti-convulsant drug, and I expect that additional compounds in hemp will gradually be shown to have therapeutic value. From this perspective, finding compounds in hemp that bind to the viral spike protein was not too surprising. However, our follow-up discovery that CBDA and CBGA can prevent SARS-CoV-2 cell entry was exhilarating.
Your data show CBDA and CBGA are effective against two COVID-19 variants. These compounds can be derived easily from hemp. There are so many directions in which you could take this research—from clinical trials with these cannabinoids to new studies of blocking virus/receptor interactions for other diseases. Can you tell us what’s next, or give us some ideas of what new avenues this research has opened up for other researchers?
Building on what is already known about the safety and bioavailability of CBDA and CBGA, clinical research should be able to advance quickly to clinical trials that can add to our knowledge of pharmacokinetics, safety, and efficacy of these cannabinoids. We hope to contribute to these studies.
We look forward to seeing you present this work and updates at the analytical keynote address at the 2022 Cannabis Science Conference in Long Beach, CA on May 20th. In closing, is there anything that you would like to share with our readers?
I would like to thank my collaborator Tafesse Fikadu and his team at Oregon Health & Science University who generously carried out the testing of CBDA and CBGA using live virus. This research was funded by university sources and donors to our laboratory. In addition to our donors, I would like to thank Shimadzu Scientific Instruments for high-resolution mass spectrometry support and EmerTher for providing the magnetic microbeads used for screening.
Richard Van Breemen received his BA in chemistry from Oberlin College and PhD in pharmacologyfrom Johns Hopkins University. After post doctoral research in biomedical mass spectrometry at Johns Hopkins, he taught at North Carolina State University and the University of Illinois before joining Oregon State University in 2018.
Josh Crossney is the columnist and editor of “Cannabis Crossroads” and a contributing editor to Cannabis Science and Technology® magazine. Crossney is also the founder of Cannabis Science Conference and now serves as Director of Cannabis Events at MJH Life Sciences. Direct correspondence to: Josh@JoshCrossney.com
J. Crossney, Cannabis Science and Technology 5(2), 22-23 (2022).