Reactive oxygen species promotion drives auranofin’s antiviral activity against hepatitis E virus

Hepatitis E virus (HEV) lacks approved virus-specific antiviral therapies, and off-label treatments with ribavirin and pegylated interferon are limited by toxicity and emerging resistance mutants. This study identifies reactive oxygen species (ROS) promotion mediated by the FDA-approved drug auranofin and D-amino acid oxidase as an effective antiviral strategy against multiple genotypes of HEV, including two globally relevant human-associated genotypes and a ribavirin treatment failure-associated HEV mutant. The observed synergistic anti-HEV activity <i>in vitro</i> for combined treatment with both auranofin and ribavirin suggests a potential clinically effective combinational therapeutic approach. ROS promotion through auranofin or other means represents an underexplored antiviral strategy with potential for broad-spectrum activity against a range of viral diseases.