Researchers in the United States have conducted a study showing that a cannabis plant compound inhibited severe acute coronavirus 2 respiratory syndrome (SARS-CoV-2) infection in human lung cells.
SARS-CoV-2 is the agent responsible for the 2019 coronavirus disease pandemic (COVID-19) that continues to sweep the globe, posing a threat to global public health and the global economy.
Marsha Rosner of the University of Chicago and Illinois and her colleagues found that cannabidiol (CBD) and its metabolite 7-OH-CBD strongly blocked SARS-CoV-2 replication in lung epithelial cells.
CBD inhibited viral gene expression and reversed many of the effects that the virus has on host gene transcription.
The compound also induced the expression of interferons – cellular signaling proteins that are produced by host cells in early response to viral invasion.
Moreover, the incidence of SARS-CoV-2 infection was up to a smaller order in a cohort of patients who took CBD compared to patients who did not take CBD.
“This study highlights CBD and its active metabolite, 7-OH-CBD, as potential preventive agents and therapeutic treatments for SARS-CoV-2 in the early stages of infection,” says Rosner and the team.
A pre-printed version of the research paper is available on bioRxiv* server, while the article is subject to peer review.
The rapid spread of SARS-CoV-2 highlights the need for new treatments
Since the onset of the COVID-19 outbreak in Wuhan, China, in late December 2019, the rapid spread of SARS-CoV-2 has led to over 119.5 million infections and caused more than 2.64 million deaths.
Although recently approved vaccines are now being released in many countries, the virus is still spreading rapidly. Rosner and colleagues say this highlights the need for alternative approaches, especially among populations with limited access to vaccines.
However, “to date, few therapies have been identified that block SARS-CoV-2 replication and viral production,” the researchers write.
More about SARS-CoV-2 and CBD
The SARS-CoV-2 virus mainly enters host cells by binding to a surface viral protein called the angiotensin 2 conversion enzyme (ACE2), a receptor on the human host cell.
The viral genome is then translated into two large polypeptides that are cleaved by the MPro and PLPro viral proteases to produce the proteins needed for viral replication, assembly, and budding.
Rosner and colleagues say that although limited, some studies have reported that certain cannabinoids have antiviral effects against hepatitis C virus and other viruses.
Moreover, an oral CBD solution is already approved by the US Food and Drug Administration for the treatment of epilepsy.
The use of high-dose CBD in patients is significantly correlated with a decrease in COVID-19 positivity. Associations between the reported use of cannabinoid drugs and the results of the COVID-19 test in adults tested at the University of Chicago Medicine (total n = 93,565). P *: p values of the specified percentage of population positivity compared to the percentage of positivity of all patients (10% COVID-19 positive in 93,565 patients). Middle right: 85 patients took CBD before the COVID test date. Top right: 82 of the 85 patients took FDA-approved CBD (Epidiolex®) and were matched with 82 of the 93,167 patients (appropriate controls) with a pattern of the nearest neighbor who scored the patients. depending on demographics and diagnoses and medications recorded in the two years prior to the COVID-19 test. P-values were calculated using Fisher’s two-sided exact test.
What did the current study involve?
To test the effect of CBD on SARS-CoV-2 replication, the researchers pretreated A549 human lung carcinoma cells expressing ACE-2 (A549-ACE2) with 0-10 μM CBD for 2 hours before infecting them with SARS- CoV-2.
Cell analysis 48 hours later showed that CBD strongly inhibited viral replication in cells.
Because CBD is often consumed as part of Cannabis sativa extract, the team investigated whether other cannabinoids could inhibit SARS-CoV-2 infection, especially those with tightly bound structures.
Remarkably, the only agent that strongly inhibited viral replication was CBD; limited or no antiviral activity was shown by the other structurally similar cannabinoids tested.
Furthermore, the metabolite CBD 7-OH-CBD, the active ingredient in the treatment of CBD epilepsy, effectively inhibited SARS-CoV-2 replication in A549-ACE2 cells.
CBD effectively eliminated viral RNA expression
When the researchers evaluated whether CBD could prevent proteolytic cleavage of Mpro or PLpro, they found that CBD had no effect on the activity of both proteases.
This led the team to hypothesize that CBD targets host cell processes.
Consistent with this hypothesis, RNA sequencing of infected A549-ACE2 cells treated with CBD for 24 hours revealed significant suppression of SARS-CoV-2-induced changes in gene expression.
CBD effectively eliminated viral RNA expression, including RNA encoding spike protein.
Both SARS-CoV-2 and CBD triggered significant changes in cell gene expression, including the expression of several transcription factors.
Further analysis of the host cell RNA showed that the virus-induced changes were almost completely reversed, but rather than cells returning to a normal cellular state, CBD + virus-infected cells resemble those treated with CBD alone.
What about interferon signaling?
Because SARS-CoV-2 infection is known to suppress the interferon signaling pathway, the researchers tested whether CBD could suppress viral infection by introducing this pathway.
Some genes have been induced by CBD in both the absence and presence of SARS-CoV-2, including genes encoding interferon receptors and mediators of the interferon signaling pathway.
In addition, CBD has effectively reversed the viral induction of cytokines that can trigger a deadly hyperinflammatory response called the “cytokine storm” in the later stages of infection.
“Thus, CBD has the potential not only to act as an antiviral agent in the early stages of infection, but also to protect the host against a hyperactive immune system in later stages,” says Rosner and the team.
The incidence of SARS-CoV-2 was lower in patients taking CBD
Finally, the team assessed the incidence of SARS-CoV-2 infection in 82 patients who were prescribed CBD prior to SARS-C0V-2 testing and associated patients who were not prescribed CBD.
Surprisingly, the incidence of SARS-CoV-2 was only 1.2% among patients prescribed CBD, compared with 12.2% among patients who did not take CBD.
“Substantially reducing the risk of SARS-CoV-2 infection by approximately one order of magnitude in patients taking FDA-approved CBD highlights the potential effectiveness of this drug in fighting SARS-CoV2 infection,” says Rosner and colleagues.
“We support placebo-controlled clinical trials, with known concentrations and highly characterized formulations, to define the role of CBD in the prevention and treatment of early SARS-CoV-2 infection,” they conclude.
*Important Note
bioRxiv publishes preliminary scientific reports that are not evaluated by colleagues and therefore should not be considered conclusive, guide clinical practice / health-related behavior or be treated as established information.