Introduction: Infections attributed to number of respiratory viruses are a major cause of morbidity and mortality worldwide. Increasing data suggests that host genetic variants are important for the susceptibility to respiratory viruses. Genes and pathways that may modify viral pathogenesis can be identified leading to new therapeutic targets to treat viral infection.

Objectives: To interrogate genetic association signals to identify novel genes and pathways important in host-virus interactions and identify therapeutic opportunities.

Methods: Using literature search, genetic signals which showed association with host-rhinovirus (RV), respiratory syncytial virus (RSV), and SARS-CoV-2 interactions were obtained. A previously developed pipeline was used to score casual genes from genetic signals using databases (Portelli, M.A. et al., Front. Allergy 2021; 2:738741). Analysis of diseases and drug-gene interaction were conducted.

Results: We identified 20, 107 and 95 causal genes of potential interest for RV, RSV and SARS-CoV-2 respectively. For RV and RSV, immunomodulatory pathways may be particularly important. For SARS-CoV-2, the antigen presentation pathway was highlighted. Distinct and overlapping genes identified for the three viruses suggests scope to treat multiple infections targeting the same genes/pathways. Drugs targeting the candidate casual genes that are currently in Phase II, III or IV of clinical trials were identified.

Conclusions: Identification of candidate genes for respiratory viruses gives insight into mechanisms important for host-virus susceptibility and may serve as druggable targets to treat viral infections.