Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants
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High Resolution Image Download MS PowerPoint Slide 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.
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Both native and affinity MS approaches have been applied with single compounds as well as substrate pools, allowing simultaneous screening of complex natural compound libraries.
“Both native and affinity MS approaches have been applied with single compounds as well as substrate pools, which allows for the simultaneous screening of complex natural compound libraries26–28.”
From Native metabolomics identifies the rivulariapeptolide family of protease inhibitors (2022) · cites this paper as [27]
The Experimental Section (Affinity Selection–Mass Spectrometry; page not provided) reports screening individual cannabinoid standards, mixtures of standards, and extracts using affinity-selection MS. Results and Discussion says this approach is suited to screening natural-product mixtures. The paper does not establish the claim about native MS approaches. (LLM, conf=0.86)
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- Authors
- van Breemen, R. B., Muchiri, R. N., Bates, T. A., Weinstein, J. B., Leier, H. C., Farley, S., & Tafesse, F. G.
- Affiliations
- Linus Pauling Institute, Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2900 SW Campus Way, Corvallis, Oregon 97331, United States
- Oregon State University (US)
- Oregon Health & Science University (US)
- ORCID
- Venue
- Journal of Natural Products
- Publisher
- American Chemical Society (ACS)
- Published
- 2022-01-10
- Volume
- 85
- Issue
- 1
- Pages
- 176-184
- ISSN
- 0163-3864 (ISSN-L)
- 1520-6025
- PMC
- PMC8768006
- OpenAlex
- W4205758030
- Cited by
- 135
- References
- 44
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 34 · 2023: 40 · 2022: 41
- FWCI
- 15.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Natural Products (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T32HL083808)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Medicinal Plant Research
- Keywords
- cannabinoids, SARS-CoV-2, COVID-19 pandemic, SARS-CoV-2 spike protein, cannabigerolic acid, cannabidiolic acid, hemp, Cannabis sativa, affinity selection-mass spectrometry, viral entry inhibition, B.1.1.7 variant, B.1.351 variant
- MeSH terms
- Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Animals, Antiviral Agents, Benzoates, Cannabinoids, Chlorocebus aethiops, Humans, Ligands, Models, Molecular, Protein Binding, Mass Spectrometry, Vero Cells, Virus Internalization, Spike Glycoprotein, Coronavirus
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