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Authors: Olga Kovalchuk et al.

Link to paper: https://www.preprints.org/manuscript/202004.0315/v1

Journal/ Pre-Print: Preprints

Key Words: COVID-19; SARS-CoV2; ACE2 receptor; medical cannabis; CBD

Research Highlights

· Identification of 13 high-Cannabinoid cannabidiol (CBD) C.sativa extracts that modulate ACE2 gene expression and protein levels in artificial 3D models of oral, airway and intestinal human tissues.

· Some high-CBD C.sativa extracts down-regulate serine protease TMPRSS2.

· High-CBD C.sativa extracts may be used for diminishing COVID-19 transmission and as adjunct to the chosen treatment.

Summary 

Entry of the SARS-COV-2 virus is mediated by the ACE2 receptor. Modulation of ACE2 receptor expression could therefore reduce disease susceptibility. Cannabinoid cannabidiol (CBD) has been shown to alter gene expression harbours anti-inflammatory properties. Using 3D models of oral, airway and intestinal tissues, Kovalchuk et al. identified 13 out of 800 Cannabis sativa lines that contained high levels of CBD capable of decreasing gene and protein expression of ACE2 and TMPRSS2, a serine protease also required for SARS-COV-2 viral entry. The researchers propose high CBD C. sativa as a potential adjunct therapeutic to decrease oral viral entry.

Impact for SARS-CoV2/COVID19 research efforts

Inhibit of SARS-CoV2/COVID19 transmission: Authors purpose C.sativa extract mouth wash as a preventative treatment to be carried out at home.

Treat of SARS-CoV2/COVID19 positive individuals: C.sativa extract mouth wash could be employed as an adjunct to theraphy.

Study Type

· Testing of different Cannabis sativa lines and extracts for in in vitro 3D organoid study containing human-derived human cells.

Strengths and limitations of the paper

Novelty: Identification of C. sativa extracts that can regulate the expression of ACE2 receptor.

Standing in the field: As far as we are aware, this is the first paper to suggest cannabinoids can regulate the expression of the ACE2 receptor.

Appropriate statistics: No. Only 2 samples used in the majority of this paper for each group. Therefore, students t-test is likely not possible.

Viral model used: No viral model used. Tissue models: EpiAirwayTM, EpiOralTM, EpiIntestinalTM tissues (Mattek Life Sciences).

Translatability: Authors suggest that oral mouthwashes containing the highest performing CBD extracts could be used to inhibit viral entry by decreasing expression of ACE2. However, they showed decreased expression of ACE2 in 3D organoids as a result of 24-hour exposure to CBD. Therefore, translatability is questionable. They also do not show how viral entry is affected subsequent to down regulation of ACE2 expression in 3D organoids.

Main limitations: Limited n number. Quantification not robust. Stats from n=2? Unclear HPLC analysis of C.sativa extracts and poor characterisation of the ratio between the various components of the plant extract. No ladder on western blot. ECL quantification difficult as GAPDH control is not clear.