Functional variation (Q63R) in the cannabinoid CB2 receptor may affect the severity of COVID-19: a human study and molecular docking

• Published in: Archives of virology 2021-11, Vol.166 (11), p.3117-3126
• Main Authors: Rastegar, Mostafa, Samadizadeh, Saeed, Yasaghi, Mohammad, Moradi, Abdolvahab, Tabarraei, Alijan, Salimi, Vahid, Tahamtan, Alireza
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cannabinoid CB2 receptors; Case-Control Studies; Coronaviruses; COVID-19; COVID-19 - diagnosis; COVID-19 - genetics; Female; Gene Frequency; Genetic diversity; Genetic Predisposition to Disease - genetics; Genotype; Genotypes; GTP-Binding Proteins - metabolism; Heredity; Humans; Immune system; Infectious Diseases; Inflammatory diseases; Iran; Male; Medical Microbiology; Middle Aged; Models, Molecular; Molecular Docking Simulation; Molecular modelling; Original; Original Article; Patients; Polymorphism, Genetic; Protein Binding; Receptor, Cannabinoid, CB2 - chemistry; Receptor, Cannabinoid, CB2 - genetics; Receptor, Cannabinoid, CB2 - metabolism; SARS-CoV-2; Severity of Illness Index; Virology
• ISSN: 0304-8608; 1432-8798; 1432-8798
• DOI: 10.1007/s00705-021-05223-7

Evidence supports a role of host genetic diversity in the clinical course of coronavirus disease 2019 (COVID-19). Variation in the cannabinoid CB2 receptor gene ( CNR2 ) could affect the regulatory action of endocannabinoids on the immune system, resulting in an increased risk of various inflammatory diseases. The present study investigated the relationship between the CNR2 -Q63R variant and COVID-19 severity. A total of 200 Iranian COVID-19 patients were enrolled in the study and genotyped using a TaqMan assay. The co-dominant, dominant, recessive, over-dominant, and additive inheritance models were analyzed using SNPStats software. In silico molecular docking was also performed to simulate the effects of the Q63R variation on CB2 binding with a ligand and with the G-protein. A significant difference in the Q63R allele and genotype distribution was found between expired and discharged COVID-19 patients in co-dominant, recessive, and additive inheritance models. The molecular docking results showed that the predicted structure of mutant CB2 (63R type) could not bind to the G-protein in the correct position. The data indicated that the Q63R variation in the CNR2 gene may affect the severity of COVID-19. Identification of genes related to susceptibility and severity of COVID-19 may lead to specific targets for drug repurposing or development. Graphic abstract