Researchers in the United States have conducted a study showing that a cannabis plant compound inhibits infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human lung cells.
SARS-CoV-2 is the agent responsible for the coronavirus pandemic 2019 (COVID-19) that continues to spread worldwide and pose a threat to the global public health and the global economy.
Marsha Rosner of the University of Chicago at Illinois and colleagues found that cannabidiol (CBD) and its metabolite 7-OH-CBD potentially block SARS-CoV-2 replication in lung epithelial cells.
The CBD inhibited viral gene expression and reversed many of the effects that the virus has on host transcription.
The compound also induced the expression of interferons – cell signaling proteins produced by host cells as an early response to viral invasion.
Furthermore, the incidence of SARS-CoV-2 infection was up to an order of magnitude lower in a group of patients taking CBD compared with patients not having CBD.
“This study highlights downtown and its active metabolite, 7-OH downtown, as possible preventative agents and therapeutic treatments for SARS-CoV-2 in early stages of infection,” Rosner and the team say.
A preview version of the research article is available on the bioRxiv* server, while the article is being peer-reviewed.
The rapid spread of SARS-CoV-2 underscores the need for new treatments
Since the outbreak of COVID-19 first began in Wuhan, China, in late December 2019, the rapid spread of SARS-CoV-2 has led to more than 119.5 million infections and caused more than 2.64 million deaths.
Although recently approved vaccines are being rolled out in many countries, the virus is still spreading rapidly. Rosner and colleagues say it underscores the need for alternative approaches, especially among populations with limited access to vaccines.
“To date, however, a few therapies have been identified that block SARS-CoV-2 replication and viral production,” the researchers write.
More about SARS-CoV-2 and SSK
The SARS-CoV-2 virus enters mainly host cells by binding a surface viral protein called spike to the human host receptor angiotensin-converting enzyme 2 (ACE2).
The viral genome is then translated into two large polypeptides which are cleaved by the viral proteases MPro and PLPro to produce the proteins required for viral replication, assembly and germination.
Rosner and colleagues say that, although limited, some studies have reported that certain cannabinoids have antiviral effects against hepatitis C virus and other viruses.
Furthermore, an oral solution from downtown has already been approved by the U.S. Food and Drug Administration for the treatment of epilepsy.
The use of high doses of CBD in patients has been significantly correlated with a reduction in COVID-19 positivity. Relationships between reported cannabinoid medication use and COVID-19 test results in adults tested at the University of Chicago Medicine (total n = 93,565). P *: p values of percent positivity of the specified patient population compared to percent positivity of all patients (10% COVID-19 positive among 93,565 patients). Right in the middle: 85 patients took downtown before their COVID test date. Top right: 82 of the 85 patients took the FDA-approved Downtown (Epidiolex®) and linked to 82 of the 93,167 patients (Matched Controls) with a nearest neighborhood propensity model that patients score according to their demographics and their recorded diagnoses and medications has. of the two years before their COVID-19 test. P-values were calculated using Fisher’s exact test two-sided.
What did the current study involve?
To test the effect of CBD on SARS-CoV-2 replication, the researchers treated A549 human lung carcinoma cells that pretreated ACE-2 (A549-ACE2) with 0-10 μM CBD for up to 2 hours before using SARS -CoV-2 is contaminated.
Analysis of the cells 48 hours later showed that CBD strongly inhibited viral replication in the cells.
Since downtown is often consumed as part of a Cannabis sativa extract, the team investigated whether other cannabinoids could also inhibit SARS-CoV-2 infection, especially those with closely related structures.
Remarkably, the CBD was the only agent that strongly inhibited viral replication. limited or no antiviral activity was exhibited by the other structurally similar cannabinoids tested.
Furthermore, the CBD metabolite 7-OH-CBD, the active ingredient in the downtown treatment of epilepsy, also effectively inhibited SARS-CoV-2 replication in the A549-ACE2 cells.
CBD effectively eliminates viral RNA expression
When the researchers assessed whether CBD could prevent proteolytic cleavage by Mpro or PLpro, they found that CBD had no effect on the activity of one protease.
This led to the team assuming that the city center was focused on hosting processes.
Consistent with this hypothesis, RNA sequencing of infected A549-ACE2 cells treated with CBD for 24 hours showed significant suppression of SARS-CoV-2-induced changes in gene expression.
The CBD effectively eliminated viral RNA expression, including RNA encoding the vein protein.
Both SARS-CoV-2 and CBD caused significant changes in cellular gene expression, including the expression of several transcription factors.
Further analysis of host cell RNA showed that the virus-induced changes were almost completely reversed, but rather than returning the cells to a normal cell state, the CBD + virus-infected cells resembled those treated with CBD alone is.
What about interferon signal?
Since infection with SARS-CoV-2 is known to suppress the interferon signaling pathway, the researchers tested whether CBD can suppress viral infection by setting this pathway.
Some genes have been induced by the 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 effectively reversed the viral induction of cytokines causing a deadly hyperinflammatory response called the “cytokine storm” during the later stages of infection.
“CBD therefore has the potential to act not only as an antiviral agent in the early stages of infection, but also to protect the host at later stages from an overactive immune system,” Rosner and the team say.
The incidence of SARS-CoV-2 was lower in patients using downtown
Finally, the team assessed the incidence of SARS-CoV-2 infection among 82 patients prescribed CBD before the SARS-C0V-2 test and matched patients who were not prescribed CBD.
Remarkably, the incidence of SARS-CoV-2 was only 1.2% among the patients who prescribed CBD, compared with 12.2% among the patients who did not have CBD.
“The significant reduction in SARS-CoV-2 infection risk by approximately an order of magnitude in patients taking the FDA-approved CBD highlights the potential efficacy of this drug in combating SARS-CoV2 infection,” says Rosner. a colleague.
“We advocate carefully designed, placebo-controlled clinical trials with known concentrations and strongly characterized formulations to define the role of CBD in the prevention and treatment of early SARS-CoV-2 infection,” they conclude.
* Important notice
bioRxiv publishes preliminary scientific reports that are not judged by peers, and therefore should not be considered conclusive, should guide clinical practice / health-related behavior, or be treated as established information.