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

In the 2019 study, researchers aimed to repurpose FDA-approved drugs as novel inhibitors for influenza A(H1N1)pdm09 by analyzing clinical gene expression profiles from infected patients. They screened 1,309 drugs, shortlisting 35 with significant in vitro antiviral activity. Diltiazem, a hypertension drug, was identified as a promising candidate due to its ability to modulate host antiviral response genes and cholesterol metabolism. In vivo testing in mice showed that diltiazem improved survival rates and reduced lung viral titers, with 40% survival at full dose and 20% at half dose, compared to 50% in control groups. Combining diltiazem with oseltamivir, an existing antiviral, enhanced efficacy. The study concluded that diltiazem has potential as a host-targeted antiviral for influenza, and a Phase II clinical trial was rapidly authorized to test the combination of diltiazem and oseltamivir for severe influenza infections in intensive care units.