Oregon State research shows hemp compounds prevent coronavirus from entering human cells

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

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