How can hemp compounds block the COVID-19 virus infection?

Research demonstrates the ability to prevent COVID-19 from entering human cells through cannabinoid acids binding to a SARS-CoV-2 protein, blocking infection from the virus

Using a chemical screening technique invented at Oregon State University, hemp compounds identified in the study revealed the ability to prevent the virus that causes COVID-19 from entering human cells.

Known scientifically as Cannabis sativa, hemp is a source of fibre, food, and animal feed. Multiple hemp extracts and compounds are added to cosmetics, body lotions, dietary supplements, and food, which continue to increase in market demand.

Oregon State’s Global Hemp Innovation Centre and its collaborators 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.

Hemp is grown specifically for industrial or medicinal use

The study, led by Richard van Breemen, a researcher with Oregon State’s Global Hemp Innovation Centre, College of Pharmacy and Linus Pauling Institute, was published in the Journal of Natural Products.

The spike protein is the same drug target used in COVID-19 vaccines and antibody therapy, using the compounds cannabigerolic acid, or CBGA, and cannabidiolic acid, CBDA. A drug target is any molecule critical to the process a disease follows, entailing its disruption can prevent infection or progression of a disease.

van Breemen said: “These cannabinoid acids are abundant in hemp and in many hemp extracts. 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.”

The two variants highlighted are also known the alpha and beta variant. 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 non-structural proteins and several “accessory” proteins.

Hemp has previously been beneficial for patients with other viral infections, such as HIV-1 and hepatitis

van Breemen added: “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.

“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 team identified the two cannabinoid acids through a mass spectrometry-based screening technique invented, screening a range of botanicals used as dietary supplements including red clover, wild yam, hops and three species of liquorice.

Later research revealed 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.

van Breemen stated: “These compounds can be taken orally and have a long history of safe use in humans. 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.”

“We identified several cannabinoid ligands and ranked them by affinity to the spike protein. 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. 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.”

Affinity selection mass spectrometry, abbreviated to AS-MS, involves incubating a drug target like the SARS-CoV-2 spike protein with a mixture of possible ligands, or things that might bind to it, such as a botanical extract, in this case being hemp extract. The ligand-receptor complexes are then filtered from the non-binding molecules using one of several methods.

Resistant variants could still arise amid widespread use of cannabinoids, but that the combination of vaccination and CBDA/CBGA treatment should make SARS-CoV-2 much less able to enter the human body and infect people.