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 (MPro) was predicted as a primary mechanism[1]. Therefore, we conducted an in vitro anti-SARS-CoV2 MPro 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 MPro 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 MPro prediction for THC and CBD by Raj et al. (2021)[1] and suggest a different anti-SARS-CoV2 mechanism for CBN.