Assessment of antiviral potencies of cannabinoids against SARS-CoV-2 using computational and in vitro approaches

• Published in: International journal of biological macromolecules 2021-01, Vol.168, p.474-485
• Main Authors: Raj, Vinit, Park, Jae Gyu, Cho, Kiu-Hyung, Choi, Pilju, Kim, Taejung, Ham, Jungyeob, Lee, Jintae
• Format: Article
• Language: English
• Subjects: Antiviral Agents - chemistry; Antiviral Agents - pharmacokinetics; Antiviral Agents - pharmacology; Cannabidiol - chemistry; Cannabidiol - pharmacokinetics; Cannabidiol - pharmacology; Cannabinoids - chemistry; Cannabinoids - pharmacokinetics; Cannabinoids - pharmacology; Cannabinols; Computer Simulation; Coronavirus 3C Proteases - antagonists & inhibitors; Coronavirus 3C Proteases - chemistry; Coronavirus 3C Proteases - drug effects; COVID-19 - drug therapy; COVID-19 - virology; Dronabinol - chemistry; Dronabinol - pharmacokinetics; Dronabinol - pharmacology; Drug Evaluation, Preclinical; Humans; In vitro antiviral assay; In Vitro Techniques; Ligands; Models, Biological; Molecular Docking Simulation; Molecular Dynamics Simulation; Pandemics; Protease Inhibitors - chemistry; Protease Inhibitors - pharmacology; SARS-CoV-2 - chemistry; SARS-CoV-2 - drug effects; SARS-CoV-2 and Mpro enzyme
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.12.020

Effective treatment choices to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are limited because of the absence of effective target-based therapeutics. The main object of the current research was to estimate the antiviral activity of cannabinoids (CBDs) against the human coronavirus SARS-CoV-2. In the presented research work, we performed in silico and in vitro experiments to aid the sighting of lead CBDs for treating the viral infections of SARS-CoV-2. Virtual screening was carried out for interactions between 32 CBDs and the SARS-CoV-2 Mpro enzyme. Afterward, in vitro antiviral activity was carried out of five CBDs molecules against SARS-CoV-2. Interestingly, among them, two CBDs molecules namely Δ9 -tetrahydrocannabinol (IC50 = 10.25 μM) and cannabidiol (IC50 = 7.91 μM) were observed to be more potent antiviral molecules against SARS-CoV-2 compared to the reference drugs lopinavir, chloroquine, and remdesivir (IC50 ranges of 8.16–13.15 μM). These molecules were found to have stable conformations with the active binding pocket of the SARS-CoV-2 Mpro by molecular dynamic simulation and density functional theory. Our findings suggest cannabidiol and Δ9 -tetrahydrocannabinol are possible drugs against human coronavirus that might be used in combination or with other drug molecules to treat COVID-19 patients.