Multi-Omics Studies towards Novel Modulators of Influenza A Virus-Host Interaction

Abstract

Human influenza A viruses (IAVs) cause global pandemics and epidemics. These viruses evolve rapidly, making current treatment options ineffective. To identify novel modulators of IAV-host interactions, we re-analyzed our recent transcriptomics, metabolomics, proteomics, phosphoproteomics, and genomics/virtual ligand screening data. We identified 713 potential modulators targeting 199 cellular and two viral proteins. Anti-influenza activity for 48 of them has been reported previously, whereas the antiviral efficacy of the 665 remains unknown. Studying anti-influenza efficacy and immuno/neuro-modulating properties of these compounds and their combinations as well as potential viral and host resistance to them may lead to the discovery of novel modulators of IAV-host interactions, which might be more effective than the currently available anti-influenza therapeutics.

Keywords: antiviral agent; genomics; influenza virus; metabolomics; phosphoproteomics; proteomics; transcriptomics; virtual ligand screening.

Figure 1

Discovery pipeline for novel modulators of IAV–host interactions. Altogether 713 potential modulators of virus-host interactions derived from the analysis of our recent omics studies [10,11,12,13]. These molecules should be first evaluated in vitro using antiviral efficacy assays, and then in animal models as described in our previous studies [14]. The immuno-modulatory effects of these drugs should also be studied, followed by drug resistant tests as in ref. [15]. In addition, combinations of some of these compounds should be tested, to decrease their toxicity and increase efficacy as described in ref. [10].

Figure 2

An “eye diagram” showing representative pathways, proteins and compounds, which can be potentially used for modulation of IAV–host interactions. The signaling/metabolic pathways are represented as various colored circles in the middle of the eye diagram. The colored curved lines originating from the pathways connect corresponding compounds on left to target proteins on right. Only the compounds that have shorter names are included for the sake of clarity.