Graphic abstract 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.

Background: Variations in the viral receptor human angiotensin-converting enzyme 2 (ACE2) may specify the susceptibility of a certain population to severe acute respiratory syndrome coronavirus 2. Objective: Evaluation of the affinity of severe acute respiratory syndrome coronavirus 2 spike glycoprotein to the Iranian genetic variants of ACE2. Materials & methods: Single nucleotide polymorphisms of ACE2 among the Iranian population were collected from the Iranome database. Missense mutations in the N-terminal peptidase domain were selected for in silico analysis. Results: 17 missense single nucleotide polymorphisms were found at ACE2. Viral glycoprotein had the lowest affinity to ACE2 mutant V485L. Discussion: The V485L variant of ACE2 could be a natural resistance mutation among the Iranian population. In addition, variant S331F can increase slightly the susceptibility to infection with the virus.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in paediatrics. While antivirals are apparent candidates to treat RSV-induced diseases, they have not yet met expectations and have remained in infancy. There is growing evidence to suggest that modulating the exacerbated inflammation during RSV infection can improve disease outcome. Curcumin-loaded niosomes have anti-inflammatory effects against RSV-induced respiratory disease by reducing immune cells' infiltration and inflammatory cytokines' production. This study evaluated the effects of curcumin-loaded niosomes on RSV-induced immunopathology in a mice model. Curcumin-loaded niosomes were prepared using the thin-film hydration method and characterized in vitro. Female Balb/c mice were infected by RSV-A2 and treated daily with curcumin-loaded niosomes. The potential anti-inflammatory effects of curcumin-loaded niosomes were evaluated on day 5 after infection. Using curcumin-loaded niosomes decreased immune cell influx and the inflammatory mediators (MIP-1α, TNF-α and IFN-γ) production in the lung, resulting in alleviated lung pathology following RSV infection. These findings indicate that curcumin-loaded niosomes have anti-inflammatory potential and could be a promising candidate to alleviate RSV-associated immunopathology.