Repurposing of Drugs as Novel Influenza Inhibitors from Clinical Gene Expression Infection Signatures

In 2018, a study was conducted to develop and validate a strategy for repurposing existing drugs as inhibitors of influenza viruses. The researchers used global transcriptomic signatures of infection from a patient cohort to identify potential drugs, resulting in a shortlist of 35 candidates from 1,309 FDA-approved bioactive molecules. Of these, 31 were validated for their significant in vitro antiviral activity. The study highlighted diltiazem, a calcium channel blocker used for hypertension, as a promising treatment for influenza infections. The drug was found to modulate the expression of specific genes related to the host antiviral response and cholesterol metabolism. A combination treatment with diltiazem and oseltamivir neuraminidase inhibitor further increased antiviral efficacy, leading to the initiation of a Phase II clinical trial. This strategy could have major implications for managing antimicrobial resistance and responding to future epidemic or pandemic diseases.