Could marijuana prevent COVID? Cannabis compounds stop virus from entering human cells

CORVALLIS, Ore. — Could the key to beating COVID-19 be marijuana? It may sound like a cannabis user’s dream, but researchers from Oregon State University find certain hemp compounds can indeed prevent the virus that causes COVID-19 from entering human cells.

The study finds that a pair of cannabinoid acids in cannabis sativa (hemp) bind to the SARS-CoV-2 spike protein, consequently preventing a critical step in the COVID-19 infection process. More specifically, those two compounds are cannabigerolic acid (CBGA) and cannabidiolic acid (CBDA). The spike protein that those two cannabinoid acids bind to is the very same viral destination COVID-19 vaccines and antibody therapies target.

“These cannabinoid acids are abundant in hemp and in many hemp extracts,” study leader Richard van Breemen, a researcher with Oregon State’s Global Hemp Innovation Center at the College of Pharmacy and Linus Pauling Institute, says in a statement.. “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.”

Stopping the virus’ ability to replicate

The coronavirus responsible for COVID-19, SARS-CoV-2, features RNA strands encoding four main structural proteins – spike, envelope, membrane, and nucleocapsid – in addition to 16 nonstructural proteins and numerous “accessory” proteins, according to van Breemen.

“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 explains. “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.”

Virus-receptor blocking compounds have helped people in the past, HIV-1 and hepatitis patients for example, study authors say.

COVID-fighting cannabis compounds are similar to CBD

Scientists used an affinity mass spectrometry-based screening technique invented in van Breemen’s laboratory to identify the two cannabinoid acids. They also assessed a number of other botanicals, including red clover, wild yam, hops, and three species of licorice.

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

The technique used to produce these findings entails incubating a drug target, such as the SARS-CoV-2 spike protein, with a variety of possible ligands — or things that might bind to it. In this case, the ligand was hemp extract. From there, researchers filter out ligand-receptor complexes from the non-binding molecules via one of numerous methods.

“We identified several cannabinoid ligands and ranked them by affinity to the spike protein,” the study author notes. “The two cannabinoids with the highest affinities for the spike protein were CBDA and CGBA, and they were confirmed to block infection.”

Licorice compound up next as possible COVID weapon?

“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 continues. “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.”

While van Breemen concedes that new COVID variants are always possible, he believes a combination of vaccination and CBDA/CBGA treatment should make viral survival much harder 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 concludes. “However, we did not test that compound, licochalcone A, for activity against the live virus yet. We need new funding for that.”

The study is published in the Journal of Natural Products.