The study determined that cannabigerolic acid (CBGA) and cannabidiolic acid (CBDA) 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.
A recent study1 conducted by researchers at the Oregon State University’s Global Hemp Innovation Center, College of Pharmacy, and Linus Pauling Institute found that cannabinoid acids in hemp may bind to the SARS-CoV-2 spike protein, blocking a critical step in the process the virus uses to infect people. Published in the Journal of Natural Products, the study determined that cannabigerolic acid (CBGA) and cannabidiolic acid (CBDA) 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.
“These cannabinoid acids are abundant in hemp and in many hemp extracts,” said Richard van Breemen, the researcher who led the study, in a story published by Oregon State. “They are not controlled substances like THC, the psychoactive ingredient in marijuana, and have a good safety profile in humans. And our research showed the hemp compounds were equally effective against variants of SARS-CoV-2, including [alpha] variant B.1.1.7, which was first detected in the United Kingdom, and [beta] variant B.1.351, first detected in South Africa.”
The spike target is the same drug target used in COVID-19 vaccines and antibody therapies. “Any part of the infection and replication cycle is a potential target for antiviral intervention, and the connection of the spike protein’s receptor binding domain to the human cell surface receptor ACE2 is a critical step in that cycle,” explained van Breenan. “That means cell entry inhibitors, like the acids from hemp, could be used to prevent SARS-CoV-2 infection and also to shorten infections by preventing virus particles from infecting human cells. They bind to the spike proteins so those proteins can’t bind to the ACE2 enzyme, which is abundant on the outer membrane of endothelial cells in the lungs and other organs.”
The two cannabinoid acids were identified using a mass spectrometry-based screening technique invented in van Breemen’s laboratory, called affinity selection mass spectrometry. A number of other botanicals used in dietary supplements, including red clover, wild yam, hops, and three species of licorice were also screened using this method. According to van Breenan, affinity selection mass spectrometry (AS-MS) involves incubating a drug target like the SARS-CoV-2 spike protein with a mixture of possible ligands that may bind to it.
“We identified several cannabinoid ligands and ranked them by affinity to the spike protein,” van Breemen said. “The two cannabinoids with the highest affinities for the spike protein were CBDA and CGBA, and they were confirmed to block infection.”
Because the cannabinoid acids were effective against the alpha and beta variants, van Breenan argues that they may complement vaccines by preventing infection from future variants. “These variants are well known for evading antibodies against early lineage SARS-CoV-2, which is obviously concerning given that current vaccination strategies rely on the early lineage spike protein as an antigen. 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.”
1. Van Breenan R et al. “Cannabinoids block cellular entry of SARS-CoV-2 and the emerging variants.” Journal of Natural Products, Published online ahead of print on January 10, 2022