The Role of Cannabis sativa L. as a Source of Cannabinoids against Coronavirus 2 (SARS-CoV-2): An In Silico Study to Evaluate Their Activities and ADMET Properties.

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.

Prevalence of Five Commonly Analyzed Cannabinoids in Forensic Toxicology Casework from Orange County CA, USA, from 2016 to 2019.

Over the last 25 years, marijuana laws have been changing throughout the USA. California started legalizing medicinal marijuana in 1996 and has since continued to relax laws. Compared to Washington and Colorado, there are little data on how the changing laws have affected the cannabinoid detection rate in California. This paper looks at the prevalence of five cannabinoids (Δ9-tetrahydrocannabinol (THC), 11-hydroxy-tetrahydrocannabinol (hydroxy-THC), 11-nor-9-carboxy-tetrahydrocannabinol (carboxy-THC), cannabinol and cannabidiol) in Orange County, CA, from 2016 to 2019. From 2016 to 2017, after legalizing recreational marijuana, there was an increase in the presence of THC, carboxy-THC and hydroxy-THC in postmortem and major crime cases, consisting mostly of sexual assaults. However, driving under the influence of drugs (DUID) saw a slight decrease. In 2018, when shops could be licensed to sell marijuana to anyone over 21 years old, there was an increase seen in all five cannabinoids for DUID and postmortem cases. The age group from 21 to 30 years showed the most prevalent cannabinoid use in all case types for all years except in major crime cases in 2019, where <21 year-old age group was the most prevalent. Surprisingly, the >50-year-old group in death investigation cases was a close second in prevalence in all years, which differs from DUID and major crime cases.

Activity of THC, CBD, and CBN on Human ACE2 and SARS-CoV1/2 Main Protease to Understand Antiviral Defense Mechanism.

THC, CBD, and CBN were reported as promising candidates against SARS-CoV2 infection, but the mechanism of action of these three cannabinoids is not understood. This study aims to determine the mechanism of action of THC, CBD, and CBN by selecting two essential targets that directly affect the coronavirus infections as viral main proteases and human angiotensin-converting enzyme2. Tested THC and CBD presented a dual-action action against both selected targets. Only CBD acted as a potent viral main protease inhibitor at the IC50 value of 1.86 ± 0.04 µM and exhibited only moderate activity against human angiotensin-converting enzyme2 at the IC50 value of 14.65 ± 0.47 µM. THC acted as a moderate inhibitor against both viral main protease and human angiotensin-converting enzymes2 at the IC50 value of 16.23 ± 1.71 µM and 11.47 ± 3.60 µM, respectively. Here, we discuss cannabinoid-associated antiviral activity mechanisms based on in silico docking studies and in vitro receptor binding studies.