Tags: Cannabinoids; in vitro antiviral assay; SARS-CoV-2; COVID-19; Mpro enzyme; cannabidiol

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Thumbnail: This study looked at the antiviral activity of cannabinoids (CBDs) against SARS-CoV-2, the virus responsible for causing COVID-19. Using both in silico (via computer) and in vitro (in laboratory cell culture) experiments, the authors tested a number of cannabinoids against SARS-CoV-2.  They identified two CBD molecules that had potent antiviral activity against SARS-CoV-2, and inhibited infection at levels comparable to drugs chloroquine, ramdesivir, and lopinavir, suggesting that these cannabinoids might be helpful in treating patients with COVID-19.

 

The problem: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has spread uncontrollably and causes significant health complications around the world, due, in large part, to a lack of effective therapeutics. Viral infections, like SARS-CoV-2, are followed by immune activation and inflammation, and sometimes this immune response can cause unintended damage as a side effect of combating the virus. It has been well documented that immune cells throughout the body express high levels of cannabinoid receptor type 2 (CB-2). CB-2 helps regulate the immune response and may offer a target to reduce damage associated with the immune response to a viral infection. Previous studies have shown that cannabinoids, (CBDs), may reduce inflammation by acting on CB-2, suggesting that CBDs may help reduce inflammation-associated damage in COVID-19.

 

The study: With the understanding that CBDs may help reduce immune-mediated damage in SARS-CoV-2 infection, this study looked to see if CBDs would also have an effect on the virus itself. This study screened 32 CBDs and looked at their ability to bind to a critical viral protein, SARS-CoV-2 Mpro, and inhibit SARS-CoV-2 infection. Using the molecular structure of these CBDs and that of SARS-CoV-2 Mpro , the authors used in silico, methods to determine which CBD molecules would best bind to the viral protein. The top CBD candidates from this computer analysis were then tested in vitro, to check for toxicity and to see if they could reduce infection in cell culture. In cell culture, CBDs were compared against the known drugs chloroquine, ramdesivir, and lopinavir.

 

Main Points:

• CBD structures were screened for binding to SARS-CoV-2 Mpro using AUTODOCK and VINA

• Top candidate molecules were identified by their conformational stability, ligand reactivity, and stability with SARS-CoV-2 Mpro

• 5 top candidates were selected for testing

• 2 CBDs, Δ9-THC and cannabidiol, showed potent antiviral activity against SARS-CoV-2, and were able to significantly reduce infection of cells in culture

• These compounds are suggested to be dual-acting; two methods are suggested for how these compounds might inhibit SARS-CoV-2:

  • They might bind to SARS-CoV-2 Mpro and block the translation of viral proteins

  • They might reduce inflammation in the lungs by acting on CB-2

• At optimal concentrations, Δ9-THC and cannabidiol also demonstrated low toxicity in cell culture

 

Conclusions: The authors conclude that their two top CBDs, Δ9-THC and cannabidiol, are effective at binding to the SARS-CoV-2 Mpro protein and inhibiting SARS-CoV-2 infection in cell culture. They conclude that these two CBDs have a low toxicity at their effective doses and suggest that these compounds may offer a potential antiviral therapeutic for COVID-19.

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Why this is a good study:

• This study screened a number of different compounds, which increased the chance of finding a successful compound

• This work lays the groundwork for these compounds to move towards being tested in human clinical trials

 

Why this isn’t a perfect study:

• All the compounds screened are licensed products and are not readily available, which may make it difficult for follow-up studies to continue this line of study

 

What this study adds:

• This study identifies two CBD compounds that may be helpful against SARS-CoV-2

• It also suggests two potential methods for how these compounds might work in SARS-CoV-2 infection

 

What it doesn’t:

• This is a preliminary study, it does not provide any information about how effective these compounds might work in an animal model or in humans.

 

Funder:

• Korea Institute of Science and Technology (KIST) institutional program (Project No. 2Z06260 and 2V08900),

• Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, and Forestry (IPET) through the Innovational Food Technology Development Program, funded by Korean Ministry of Agriculture, Food and Rural Affairs (MAFRA)(119034-3),

• Priority Research Centers Program through the National Research Foundation (NRF) of Korea funded by the Korean Ministry of Education

 

Author conflicts: None declared