ABSTRACT
Introduction: Viral respiratory infections are a major cause of mortality and morbidity globally. Accumulating data for the importance of host genetic variants on susceptibility to respiratory viruses provides an opportunity to identify genes and pathways that may alter viral pathogenesis. This can lead to new therapeutic targets to limit viral infection. Objective(s): To complete a signal to gene/pathway analysis by interrogating multiple datasets and a drug interactions analysis to identify therapeutic opportunities. Method(s): Genetic signals showing association with host-rhinovirus (RV), respiratory syncytial virus (RSV), and SARS CoV-2 interactions were obtained from literature search. Causal genes from the signals were identified using databases and scored using our previously developed pipeline (Portelli, M.A. et al., Front. Allergy 2021;2:738741). Function, pathways, and drug-gene interaction were analysed in genes scoring 3 or higher. Result(s): Signal to gene association analysis identified 20, 103 and 60 putative causal genes of potential interest for RV, RSV and SARS CoV-2 respectively. 9 genes were common to RV/RSV, 10 to RSV/SARS-CoV-2 and 3 to RV/SARS-CoV-2. Downstream analysis identified that immunomodulatory pathways may be particularly important for RV and RSV susceptibility and the antigen presentation pathway for SARS-CoV-2. Drugs targeting the genes in Phase II, III or IV of clinical trials were identified. Conclusion(s): Identification of candidate causal genes helps give a mechanistic understanding of important hostvirus mechanisms and may serve as target for novel therapeutics or drug repurposing to treat viral infection.