<https://www.eurekalert.org/news-releases/939847>

NEWS RELEASE 11-JAN-2022
Oregon State research shows hemp compounds prevent coronavirus from
entering human cells
Peer-Reviewed Publication
OREGON STATE UNIVERSITY

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
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."

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 Muchiro 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.