Phillyrin for COVID-19 and Influenza Co-infection: A Potential Therapeutic Strategy Targeting Host Based on Bioinformatics Analysis

Background: The risk of co-epidemic between COVID-19 and influenza is very high, so it is urgent to find a treatment strategy for the co-infection. Previous studies have shown that phillyrin can not only inhibit the replication of the two viruses, but also has a good anti-inflammatory effect, which is expected to become a candidate compound against COVID-19 and influenza. Objective: To explore the possibility of phillyrin as a candidate compound for the treatment of COVID-19 and influenza co-infection and to speculate its potential regulatory mechanism. Methods: We used a series of bioinformatics network pharmacology methods to understand and characterize the pharmacological targets, biological functions, and therapeutic mechanisms of phillyrin in COVID-19 and influenza co-infection and discover its therapeutic potential. Results: We revealed potential targets, biological processes, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and upstream pathway activity of phillyrin against COVID-19 and influenza co-infection. We constructed protein-protein interaction (PPI) network and identified 50 hub genes, such as MMP9, IL-2, VEGFA, AKT, and HIF-1A. Furthermore, our findings indicated that the treatment of phillyrin for COVID-19 and influenza co-infection was associated with immune balance and regulation of hypoxia-cytokine storm, including HIF-1 signaling pathway, PI3K-Akt signaling pathway, Ras signaling pathway, and T cell receptor signaling pathway. Conclusion: For the first time, we uncovered the potential targets and biological pathways of phillyrin for COVID-19 and influenza co-infection. These findings should solve the urgent problem of co-infection of COVID-19 and influenza that the world will face in the future, but clinical drug trials are needed for verification in the future.