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

Abstract

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.

The Impact of Coronavirus Disease 2019 on Viral, Bacterial, and Fungal Respiratory Infections

“…76 Although there is no clear consensus on the implications of coinfection, one study suggests there is a potential for added harm with viral coinfection, because posttranslational changes in angiotensin-converting enzyme-2 by influenza A may increase vulnerability to lung injury and acute respiratory distress syndrome (ARDS) during coinfections. 77 Although potential targets for therapy are under investigation, 78 no single medication is known to treat both SARS-CoV-2 and influenza simultaneously, although supportive care can be given for both. Similar to influenza infections, as many as one-fifth of patients with SARS-CoV-2 are found to have coinfection or superinfection with other pathogens, which increases mortality, and these coinfections and superinfections are discussed further in this article.…”

Small molecules in the treatment of COVID-19

“… 387 Further, Lai et al discovered that phillyrin could be used to treat COVID-19 and influenza co-infection since it not only inhibits the replication of both viruses, but also possesses the ability to regulate hypoxia-cytokine storm based on bioinformatics network pharmacology analysis. 388 …”

Antiviral effects of phytochemicals against severe acute respiratory syndrome coronavirus 2 and their mechanisms of action: A review

“…Bioinformatics analysis revealed that phillyrin interacted with 192 common core targets and 25 biological pathways to treat the co‐infection of SARS‐COV‐2 and influenza virus. It was suggested that the compound activates the PI3K‐AKT, RAS, and HIF‐1 signaling pathways to regulate the body's immune and antiinflammatory effects, thereby reducing the severity of diseases caused by SARS‐COV‐2 and influenza virus infections (Lai et al, 2021 ).…”