Cannabis sativa L. is an annual herbaceous plant that belongs to the family Cannabinaceae. In this study, the potential use of forty-five
cannabinoids, previously identified from Cannabis sativa to alleviate
COVID-19 infection via prohibition of crucial SARS-CoV-2
proteins using molecular docking, was examined. In silico studies were performed on three vital
enzymes that serve as principle therapeutic targets to prevent SARS-CoV-2 replication. These
enzymes are the main
protease SARS-CoV-2 MPro,
papain-like protease SARS-CoV-2 PLpro and
angiotensin-converting enzyme 2 (ACE2). Regarding SARS-CoV-2 MPro, cannabichromanon (32) showed the best fitting within its active centers, followed by
cannabinolic acid (22) and
cannabinol (21), displaying ∆G of -33.63, -23.24, and -21.60 kcal/mol, respectively. Concerning SARS-CoV-2 PLpro, cannabichromanon (32) followed by
cannabinolic acid (22) and cannabicyclolic
acid (41) revealed the best binding within its active pockets owing to multiple bond formation with ∆G values of -28.36, -22.81, and -19.89 kcal/mol. Furthermore, cannabichromanon (32),
cannabinolic acid (22), and
cannabinol (21) showed considerable fitting within the active sites of
angiotensin-converting enzyme 2 (ACE2) evidenced by their significant ∆G values that were estimated as -41.77, -31.34, and -30.36 kcal/mol, respectively. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) evaluation was performed on the tested
cannabinoids to further explore their pharmacokinetics, pharmacodynamics, and toxicity properties. The results indicated the considerable pharmacokinetic, pharmacodynamic, and toxicity properties of
cannabinol (21),
cannabinolic acid (22), cannabichromanon (32), and cannabicyclolic
acid (41) that showed best fitting scores within the active sites of the tested
enzymes. Multivariate data analysis revealed that cannabichromanon and
cannabinolic acid showed a discriminant nature and hence can be incorporated in pharmaceutical
dosage forms to alleviate
COVID-19 infection.