Researchers in the United States have conducted a study showing that a cannabis plant compound inhibited coronavirus 2 infection with severe acute respiratory syndrome (SARS-CoV-2) in human lung cells.
SARS-CoV-2 is the agent responsible for the 2019 coronavirus disease pandemic (COVID-19) that continues to sweep the world posing a threat to global public health and the global economy.
Marsha Rosner, of the University of Chicago, Illinois, and colleagues found that cannabidiol (CBD) and its metabolite 7-OH-CBD potently block SARS-CoV-2 replication in cells. pulmonary epithelial.
CBD inhibited viral gene expression and reversed many of the effects the virus has on host gene transcription.
The compound also induced the expression of interferons: cell signaling proteins that are produced by host cells as an early response to viral invasion.
In addition, the incidence of SARS-CoV-2 infection was up to an order of magnitude lower in a cohort of patients who had been taking CBD, compared with coincident patients who had not taken 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,” state Rosner and equipment.
A pre-print version of the search document is available at bioRxiv* server, while the article is undergoing peer review.
The rapid spread of SARS-CoV-2 highlights the need for new treatments
Since the outbreak of COVID-19 in Wuhan, China, in late December 2019, the rapid spread of SARS-CoV-2 has caused more than 119.5 million infections and caused more than 2.64 millions dead.
Although recently approved vaccines are now being rolled out 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.
Learn more about SARS-CoV-2 and CBD
The SARS-CoV-2 virus primarily enters host cells by binding to a superficial viral protein called an ear to the human host cell angiotensin 2 converting enzyme (ACE2).
The viral genome is then translated into two large polypeptides that are cleaved by the viral proteases MPro and PLPro to produce the proteins needed for viral replication, assembly, and budding.
Rosner and colleagues say that while limited, some studies have reported that certain cannabinoids have antiviral effects against the hepatitis C virus and other viruses.
In addition, an oral CBD solution is already approved by the U.S. Food and Drug Administration for the treatment of epilepsy.
The use of CBD in high doses in patients correlates significantly with a reduction in COVID-19 positivity. Associations between reported cannabinoid drug use and COVID-19 test results among adults tested at the University of Chicago Medicine (total n = 93,565). P *: p values of the percentage of positivity of the specified patient population compared to the percentage of positivity of all patients (10% COVID-19 positive among 93,565 patients). Center right: 85 patients took CBD before the date of the COVID test. Top right: 82 of the 85 patients took FDA-approved CBD (Epidiolex®) and matched 82 of the 93,167 patients (matching controls) with a propensity scoring model of the nearest neighbor who rated patients according to their demographics and their diagnoses and medications recorded. of the two years prior to your COVID-19 test. P-values were calculated using Fisher’s exact two-sided test.
What did the current study involve?
To test the effect of CBD on SARS-CoV-2 replication, the researchers pre-treated A549 human lung carcinoma cells expressing ACE-2 (A549-ACE2) with 0-10 μM CBD during 2 hours before infecting them with SARS-CoV-2.
Analysis of the cells 48 hours later showed that CBD had potently inhibited viral replication in the cells.
Since CBD 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.
Surprisingly, the only agent that potently inhibited viral replication was CBD; the other structurally similar cannabinoids analyzed showed limited or no antiviral activity.
In addition, the metabolite of CBD 7-OH-CBD, the active ingredient in the treatment of epilepsy CD, also 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 rupture by Mpro or PLpro, they found that CBD had no effect on the activity of any of the proteases.
This led the team to raise the hypothesis that CBD targets host cell processes.
Based on 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 the ear protein.
Both SARS-CoV-2 and CBD triggered significant changes in cell gene expression, including the expression of several transcription factors.
Further analysis of host cell RNA showed that virus-induced changes were reversed almost completely, but instead of returning cells to a normal cell state, cells infected with the CBD + virus resembled those treated with CBD only.
What about interferon signaling?
Given that 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 were 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 effectively reversed the viral induction of cytokines that can trigger a deadly hyperinflammatory response called a “cytokine storm” during the later stages of infection.
“Therefore, 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,” say 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 among 82 patients who had been prescribed CBD before performing SARS-C0V-2 testing and matched patients who were not ls had prescribed CBD.
Surprisingly, the incidence of SARS-CoV-2 was only 1.2% among patients who received CBD, compared with 12.2% of patients who had not taken CBD.
“Substantially reducing the risk of SARS-CoV-2 infection by approximately an order of magnitude in patients taking FDA-approved CBD highlights the potential efficacy of this drug in the fight against infection by SARS-CoV2, ”says Rosner and colleagues.
“We advocate carefully designed placebo-controlled clinical trials with known concentrations and highly characterized formulations in order to define the role of CBD in the prevention and treatment of early SARS-CoV-2 infection,” they conclude.
* Important news
bioRxiv publishes preliminary scientific reports that are not reviewed by experts and therefore should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.