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

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.

COVID-19: Why does disease severity vary among individuals?

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the current pandemic, coronavirus disease 2019 (COVID-19). While all people are susceptible to the SARS-CoV-2 infection, the nature and severity of the disease vary significantly among individuals and populations. Importantly, reported disease burdens and case fatality rates differ considerably from country to country. There are, however, still uncertainties about the severity of the disease among individuals or the reason behind a more severe disease in some cases. There is a strong possibility that the severity of this disease depends on a complicated interaction between the host, virus, and environment, which leads to different clinical outcomes. The objective of this article is to point out the essential influential factors related to the host, virus, and environment affecting the clinical outcome of COVID-19.

Ten challenging questions about SARS-CoV-2 and COVID-19.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently introduced as a global public health problem by the World Health Organization (WHO). The virus outbreak has been documented around the world. Updating data in different aspects of the virus could force us to revise our idea about the main questions concerning coronavirus disease-19 (COVID-19). AREAS COVERED: Although our knowledge about the SARS-CoV-2 and COVID-19 is largely based on the very limited data, the information is growing rapidly. The renewed answers to the specific research questions concerning updating data not only reveal gaps for future research but also re-categorized our information. Here, we attempt to briefly discuss 10 important questions about SARS-CoV-2 and COVID-19. EXPERT OPINION: Since our knowledge about different aspects of SARS-CoV-2 appears to be in its infancy and is rapidly changing, the provision of the right data is more difficult in this regard. However, we try to rely on results from more extensive research to answer the main questions about this new virus. Therefore, further studies, particularly in the context of the virus pathogenesis, diagnosis, treatment, and vaccine development, are warranted.