Cannabis compound inhibits SARS-CoV-2 replication in human lung cells


Researchers in the United States have conducted a study showing that a compound from the cannabis plant inhibited coronavirus 2 (severe acute respiratory syndrome) (SARS-CoV-2) infection in human lung cells.

SARS-CoV-2 is the agent responsible for the coronavirus disease 2019 (COVID-19) pandemic that continues to ravage the world and poses a threat to global public health and the global economy.

Marsha Rosner of the University of Chicago in Illinois and her colleagues found that cannabidiol (CBD) and its metabolite 7-OH-CBD potently block the replication of SARS-CoV-2 in lung epithelial cells.

CBD inhibited the expression of viral genes and reversed many of the effects that 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.

Furthermore, 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 to matched patients who had not been taking 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,” say Rosner and the team.

A pre-printed version of the research paper is available at the bioRxiv* server while the article undergoes peer review.

Study: Cannabidiol inhibits the replication of SARS-CoV-2 and promotes the host's innate immune response.  Image Credit: Stokkete / Shutterstock

The rapid spread of SARS-CoV-2 highlights the need for new treatments

Since the COVID-19 outbreak 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 now being released in many countries, the virus is still spreading rapidly. Rosner and his colleagues say this highlights the need for alternative approaches, particularly among populations with limited access to vaccines.

However, “to date, few therapies have been identified that block the replication and viral production of SARS-CoV-2,” the researchers write.

More about SARS-CoV-2 and CBD

The SARS-CoV-2 virus primarily enters host cells through the binding of a viral surface protein called pico to the human host cell receptor angiotensin-converting enzyme 2 (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 necessary for viral replication, assembly, and budding.

Rosner and his colleagues say that, although limited, some studies have reported that certain cannabinoids have antiviral effects against the hepatitis C virus and other viruses.

Additionally, a CBD oral 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 reduction in COVID-19 positivity.  Associations Between Reported Cannabinoid Drug Use and COVID-19 Test Results Among Adults Assessed at Chicago Medical University (total

The use of high-dose CBD in patients is significantly correlated with a reduction in COVID-19 positivity. Associations Between Reported Cannabinoid Drug Use and COVID-19 Test Results Among Adults Assessed at Chicago Medical University (total n = 93,565). P *: p-values ​​for the percent positivity of the specified patient population compared to the percent positivity of all patients (10% COVID-19 positive among 93,565 patients). Middle right: 85 patients took CBD before the COVID test date. Top right: 82 of 85 patients took FDA-approved CBD (Epidiolex®) and were matched with 82 of 93,167 patients (matched controls) with a nearest neighbor propensity score model that rated patients as based on your demographics and your registered medications and diagnoses. of the two years prior to your COVID-19 test. The p-values ​​were calculated using the two-sided Fisher’s exact test.

What did the current study involve?

To test the effect of CBD on the replication of SARS-CoV-2, the researchers pretreated A549 human lung carcinoma cells expressing ACE-2 (A549-ACE2) with 0-10μM CBD for 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 tested showed limited or no antiviral activity.

Furthermore, the CBD metabolite 7-OH-CBD, the active ingredient in the treatment of epilepsy with CBD, also effectively inhibited the replication of SARS-CoV-2 in A549-ACE2 cells.

CBD effectively suppressed viral RNA expression

When the researchers evaluated whether CBD could prevent proteolytic cleavage by Mpro or PLpro, they found that CBD had no effect on the activity of either 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 a significant suppression of SARS-CoV-2-induced changes in gene expression.

CBD effectively suppressed the expression of viral RNA, including the RNA encoding the spike protein.

Both SARS-CoV-2 and CBD caused significant changes in cellular gene expression, including the expression of various transcription factors.

Further analysis of the host cell RNA showed that the virus-induced changes were almost completely reversed, but instead of the cells returning to a normal cellular state, the cells infected by the CBD + virus resembled those treated. with CBD alone.

What about interferon signaling?

Since infection with SARS-CoV-2 is known to suppress the interferon signaling pathway, the researchers tested whether CBD could suppress the viral infection by introducing this pathway.

Some genes were induced by CBD both in the absence and presence of SARS-CoV-2, including genes that encode interferon receptors and mediators of the interferon signaling pathway.

Additionally, 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 an overactive immune system in later stages,” Rosner and the team say.

The incidence of SARS-CoV-2 was lower in patients taking CBD

Finally, the team evaluated the incidence of SARS-CoV-2 infection among 82 patients who had been prescribed CBD prior to the SARS-C0V-2 trial and matched patients who had not been prescribed CBD.

Surprisingly, the incidence of SARS-CoV-2 was only 1.2% among patients prescribed CBD, compared to 12.2% among matched patients who had not been taking CBD.

“The substantial reduction in the risk of SARS-CoV-2 infection of approximately an order of magnitude in patients taking FDA-approved CBD highlights the potential efficacy of this drug in fighting SARS-CoV2 infection,” say Rosner and his colleagues. colleagues.

“We advocate carefully designed 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 news

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice / health-related behavior, or be treated as established information.

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