Anti-SARS-CoV2 M^Pro activity of THC, CBD, and CBN and their structure-activity relationship (SAR)

THC, CBD, and CBN are cannabinoids present in Cannabis sativa L. and responsible for cannabis biological activities, such as antiinflammation and antibiosis. Recently, an anti-SARS-CoV2 infection of THC, CBD, and CBN was reported from a cell-based assay by Raj et al. (2021), and anti-SARS-CoV2 main protease (M^Pro) was predicted as a primary mechanism[1]. Therefore, we conducted an in vitro anti-SARS-CoV2 M^Pro activity of THC, CBD, and CBN to confirm the predicted antiviral mechanism from this recent study[1]. As a result, THC and CBD were identified as bioactive agents with 100% SARS-CoV2 M^Pro inhibition in an in vitro assay. CBN was inactive, showing 30% inhibition only. IC₅₀ value of THC and CBD was determined at 1.8 µM for CBD and 13.1 µM for THC. Our results are partially in line with the anti-SARS-CoV2 M^Pro prediction for THC and CBD by Raj et al. (2021)[1] and suggest a different anti-SARS-CoV2 mechanism for CBN.

This finding suggests a structure-activity relationship (SAR) among THC, CBD, and CBN. Main structural features are a flexible structure with bicyclic rings (C6-C6) and a cyclohexene substitution being present in CBD. This study is the first study reporting experimental data of an in vitro anti-SARS-CoV2 M^Pro activity of THC, CBD, and CBN and their structure-activity relationship.

Publication History

Article published online:
13 December 2021

• References

• 1 Raj V., Park J.G., Cho K.-H., Choi P., Kim T., Ham J., Lee J. Int. J. Biol. Macromol. 2021, 168, 474.