A Functional Genomics-pharmacotranscriptomics Framework Identifies Host-directed Anti-influenza Agents

The effectiveness of available antiviral drugs is increasingly compromised by the rapid evolution of drug-resistant IAV strains, highlighting the urgent need for new therapeutic strategies. Here, we present an integrative host-directed drug discovery framework that combines functional genomics and pharmacotranscriptomics to systematically identify compounds with anti-IAV potential.

We first aggregated published genome-wide screens to assign each host gene a quantitative functional score reflecting its role in promoting or restricting IAV replication. These scores were then paired with gene expression profiles to estimate the overall antiviral status of host cells. Using large-scale pharmacotranscriptomic data, we screened nearly 20,000 drug-induced transcriptional signatures to identify compounds that shift host gene expression toward an antiviral state.