January 10, 2022
CORVALLIS, Ore. – Hemp compounds identified by Oregon State University research
via a chemical screening technique invented at OSU show the ability to prevent the
virus that causes COVID-19 from entering human cells.
Findings of the study led by Richard van Breemen, a researcher with Oregon State’s
Global Hemp Innovation Center, College of Pharmacy and Linus Pauling Institute,
were published today in the Journal of Natural Products.
Hemp, known scientifically as Cannabis sativa, is a source of fiber, food and animal
feed, and multiple hemp extracts and compounds are added to cosmetics, body
lotions, dietary supplements and food, van Breemen said.
Van Breemen and collaborators, including scientists at Oregon Health & Science
University, found that a pair of cannabinoid acids bind to the SARS-CoV-2 spike
protein, blocking a critical step in the process the virus uses to infect people.
The compounds are cannabigerolic acid, or CBGA, and cannabidiolic acid, CBDA, and
the spike protein is the same drug target used in COVID-19 vaccines and antibody
therapy. A drug target is any molecule critical to the process a disease follows,
meaning its disruption can thwart infection or disease progression.
“These cannabinoid acids are abundant in hemp and in many hemp extracts,” van
Breemen said. “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 variant B.1.1.7, which was first detected in the United Kingdom, and variant
B.1.351, first detected in South Africa.”
Those two variants are also known the alpha and beta variant, respectively.
Characterized by crown-like protrusions on its outer surface, SARS-CoV-2 features
RNA strands that encode its four main structural proteins – spike, envelope,
membrane and nucleocapsid – as well as 16 nonstructural proteins and several
“accessory” proteins, van Breemen said.
“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,” he said. “That
means cell entry inhibitors, like the acids from hemp, could be used to prevent SARSCoV-
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.”
Using compounds that block virus-receptor interaction has been helpful for patients
with other viral infections, he notes, including HIV-1 and hepatitis.
Van Breemen, Ruth Muchiri of the College of Pharmacy and Linus Pauling Institute
and five scientists from OHSU identified the two cannabinoid acids via a mass
spectrometry-based screening technique invented in van Breemen’s laboratory. Van
Breemen’s team screened a range of botanicals used as dietary supplements
including red clover, wild yam, hops and three species of licorice.
An earlier paper in the Journal of the American Society for Mass Spectrometry
described tailoring the novel method, affinity selection mass spectrometry, to finding
drugs that would target the SARS-CoV-2 spike protein.
In the later research, lab tests showed that cannabigerolic acid and cannabidiolic acid
prevented infection of human epithelial cells by the coronavirus spike protein and
prevented entry of SARS-CoV-2 into cells.
“These compounds can be taken orally and have a long history of safe use in
humans,” van Breemen said. “They have the potential to prevent as well as treat
infection by SARS-CoV-2. 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.”
Van Breemen explains that affinity selection mass spectrometery, which he
abbreviates to AS-MS, involves incubating a drug target like the SARS-CoV-2 spike
protein with a mixture of possible ligands – things that might bind to it – such as a
botanical extract, in this case hemp extract.
The ligand-receptor complexes are then filtered from the non-binding molecules
using one of several methods.
“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.
“One of the primary concerns in the pandemic is the spread of variants, of which
there are many, and B.1.1.7 and B.1.351 are among the most widespread and
concerning,” he added. “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.”
Van Breemen said resistant variants could still arise amid widespread use of
cannabinoids but that the combination of vaccination and CBDA/CBGA treatment
should make for a much more challenging environment for SARS-CoV-2.
“Our earlier research reported on the discovery of another compound, one from
licorice, that binds to the spike protein too,” he said. “However, we did not test that
compound, licochalcone A, for activity against the live virus yet. We need new funding
for that.”
Timothy Bates, Jules Weinstein, Hans Leier, Scotland Farley and Fikadu Tafesse of
OHSU also contributed to the cannabinoid study.
About the OSU College of Pharmacy: The College of Pharmacy prepares students of today to be the
pharmacy practitioners and pharmaceutical sciences researchers of tomorrow by contributing to improved
health, advancing patient care and the discovery and understanding of medicines.
STORY BY:
Steve Lundeberg, 541-737-4039
steve.lundeberg@oregonstate.edu
SOURCE:
Richard van Breemen, 541-737-5078
Richard.vanbreemen@oregonstate.edu