Separate research programs in the US and Canada have discovered cannabinoids could prove crucial in the battle against Covid-19.
Oregon State University researchers examined cannabinoid acids CBGA and CBDA with study lead Richard van Breemen and his team finding the acids bind to the SARS-CoV-2 spike protein, blocking a critical step in the process the virus uses to infect people.
The spike protein is the same drug target used in Covid vaccines and antibody therapy.
Van Breemen said: “These cannabinoid acids are abundant in hemp and in many hemp extracts. Our research showed [they] were equally effective against variants of SARS-CoV-2, including variant B.1.1.7 first detected in the UK, and variant B.1.351 first detected in South Africa.”
Those variants are more widely known as alpha and beta, respectively.
Characterised 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 added.
“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.”
Laboratory tests showed CBGA and CBDA 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.”
Van Breemen explained the team used a process called affinity selection mass spectrometery, which involves incubating a drug target like the SARS-CoV-2 spike protein with a mixture of possible ligands – things that might bind to it – in this case hemp extract. The ligand-receptor complexes are then filtered from the non-binding molecules.
“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.”
He said the findings could help prevent the emergence and spread of other variants.
“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 shows 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 warned resistant variants could still arise amid widespread use of cannabinoids, but that the combination of vaccination and CBDA/CBGA treatment should create a much more challenging environment for SARS-CoV-2.
Meanwhile, researchers at Canada’s University of Waterloo have found synthetic cannabidiol (CBD) appears to prime the innate immune system of cells, potentially offering protection against pathogens such as SARS-CoV-2.
The team discovered synthetic cannabidiol augments the anti-viral response of cells to three key proteins produced by the SARS-CoV-2 genome after studying the proteins in human kidney cells, both alone and in combination with CBD, as well as the effects of CBD in healthy control cells.
Lead investigator Associate Professor Robin Duncan said: “When cells in the lungs or the digestive tract are infected with a virus, they have an ability to sense and respond, even before the immune system notices a virus is present.
“They do this by activating innate responses inside of cells, which form the first line of defence. In the case of Covid-19, however, this response isn’t very good, which has contributed to high infection rates.
“With an RNA-type virus like SARS-CoV-2, cells should activate an innate system that cuts up the viral genome, which also causes infected cells to undergo a process called apoptosis – a sort of controlled cell death that gets rid of infected cells early on.
“This could stop an infection, or slow its spread in the body or to others. When we combined CBD with these viral proteins, they had a much better ability to activate this system and to activate apoptosis.”
Duncan said what was potentially even more exciting was that in cells that had not been exposed to the SARS-CoV-2 proteins, CBD in therapeutic amounts seemed to prime the innate anti-viral system of cells, increasing their readiness to respond to viral infection – and that this happened without activating apoptosis in healthy cells.
Waterloo’s postdoctoral fellow Maria Fernandes, who performed the cell studies, said: “This suggests CBD at the right dose could help cells be in a better state of readiness to respond to a virus, but it doesn’t cause a response unless there is a need.”
Duncan said this idea is supported by evidence from users of a high-dose pharmaceutical CBD licensed in the US for the treatment of rare types of epilepsy. In that study, patients taking prescription high-dose synthetic CBD had around a 10-fold lower risk of testing positive for Covid-19.
A pre-peer-reviewed version of the study — ‘Cannabidiol and the anti-viral response to SARS-CoV-2 proteins’ — is published on BioRxiv.org, and is under review in the journal Life Sciences.