Researchers in the United States have conducted a study showing that cannabis plant fertilizer inhibited infection with severe acute respiratory coronavirus 2 (SARS-CoV-2) syndrome in human lung cells.
SARS-CoV-2 is the agent responsible for the 2019 coronavirus (COVID-19) pandemic outbreak that continues to wreak havoc and threaten 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 inhibited the reproduction of SARS-CoV-2 in lung epithelial cells.
CBD inhibited viral gene expression and reversed many of the effects of the virus on host gene transcription.
The fertilizer also triggered the expression of interferons – cell signaling proteins produced by host cells in early response to a viral attack.
Moreover, the incidence of SARS-CoV-2 infection was up to a lower order of magnitude in a cohort of patients who had been taking CBD, compared with patients who had not been matched. on taking CBD.
“This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential protective agents and therapeutic therapies for SARS-CoV-2 in early stages of the disease,” says Rosner and the team.
A pre-printed version of the research paper can be found on the bioRxiv* server, while the article is subject to peer review.
The rapid release of SARS-CoV-2 highlights the need for new treatments
Since the COVID-19 revolution first began in Wuhan, China, at the end of 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 distributed in many countries, the virus is still spreading rapidly. Rosner and colleagues say this highlights the need for alternative approaches, especially among numbers with limited access to vaccines.
However, “to date, few treatments have been identified that inhibit SARS-CoV-2 reproduction and viral production,” the researchers wrote.
More about SARS-CoV-2 and CBD
The SARS-CoV-2 virus mainly enters host cells by binding a superficial viral protein called a spike to the human host cell receptor angiotensin-converting enzyme 2 (ACE2).
The viral genome is then converted to two major polypeptides cleared by the viral proteases MPro and PLPro to produce the proteins necessary for viral reproduction, aggregation, and budding.
Rosner and colleagues say that, although limited, some studies have reported that some cannabinoids have antiviral effects against hepatitis C virus and other viruses.
In addition, an oral solution of CBD has already been approved by the U.S. Food and Drug Administration for the treatment of epilepsy.
The use of high-dose CBD in patients has been strongly associated with a reduction in the COVID-19 condition. Associations between reported cannabinoid drug use and COVID-19 test results among adults tested at the University of Chicago Medical Center (total n = 93,565). P *: p-values of visibility in the percentage of the named patient population compared to posterior percent of all patients (10% COVID-19 positive among 93,565 patients). Right to center: 85 patients took CBD before their COVID test date. Top right: 82 patients took 85 FDA-approved CBD (Epidiolex®) and 82 of the 93,167 patients (Equivalent Controls) were matched with the score model closest neighbor biases that rated patients according to their demographics and their documented diagnoses and medications. from the two years prior to their COVID-19 test. P-values were calculated using Fisher’s true two-sided experiment.
What did the current study cover?
To test the effect of CBD on SARS-CoV-2 reproduction, the researchers pretreated A549 human lung carcinoma cells inactivated ACE-2 (A549-ACE2) with 0–10μM CBD for 2 h before they applied SARS-CoV-2.
Examination of the cells 48 hours later showed that CBD had a strong inhibition of viral reproduction in the cells.
Because CBD is often consumed as part of a Cannabis sativa section, the team investigated whether other cannabinoids could prevent SARS-CoV-2 infection, particularly those with closely related structures.
Surprisingly, CBD was the only agent that strongly inhibited viral reproduction; antiviral activity was limited or non-existent with the other structurally similar cannabinoids.
In addition, the metabolite CBD 7-OH-CBD, the active ingredient in the treatment of CBD on epilepsy, effectively inhibited SARS-CoV-2 reproduction in the A549-ACE2 cells.
CBD effectively eliminated viral RNA definition
When the researchers evaluated whether CBD could inhibit proteolytic use with Mpro or PLpro, they found that CBD had no effect on either protease activity.
This led the team to hypothesize that CBD targets host cell processes.
Consistent with this hypothesis, the RNA sequence of CBD-treated infectious A549-ACE2 cells for 24 h showed that they suppressed SARS-CoV-2-induced changes in gene expression.
The CBD effectively eliminated the definition of viral RNA, including RNA coding for the spike protein.
Both SARS-CoV-2 and CBD induced significant changes in cell gene expression, including expression of several transcription factors.
Further analysis of host cell RNA showed that the virus-induced changes were completely reversed, but instead of the cells returning to a normal cell state, the CBD + viral cells were similar. those treated with CBD only.
What about interferon symptoms?
Because SARS-CoV-2 infection is known to suppress the interferon signaling pathway, the researchers tested whether CBD could prevent viral infection by ingesting the drug. this way.
Some genes have been implicated in CBD both in the absence and in the presence of SARS-CoV-2, including genes encoding interferon receptors and mediators of the interferon signaling pathway.
In addition, CBD effectively inhibited the viral entry of cytokines that stimulate a lethal hyperinflammatory response known as the “cytokine storm” at later stages of the disease.
“Thus, CBD has the potential not only to be an antiviral agent in early stages of the disease but also to protect the host against an immune system at later stages,” says Rosner and team. .
The frequency of SARS-CoV-2 was lower in patients who took 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 test and matched patients who had not been prescribed CBD.
Interestingly, the incidence of SARS-CoV-2 was only 1.2% among CBD-prescribed patients, compared with 12.2% among matched patients who had not been taking CBD.
“The significant reduction in the risk of SARS-CoV-2 infection around an order of magnitude in patients who have taken FDA-approved CBD highlights the effectiveness of this drug in potentially combating SARS infection. -CoV2, ”said Rosner and colleagues.
“We propose carefully controlled placebo-controlled clinical trials with known densities and fully defined shapes to elucidate the role of CBD in the prevention and treatment of early SARS-CoV-2 infection,” they end.
* Important message
bioRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.