Quercetin inhibits herpes simplex virus 1 replication in corneal epithelium and suppresses keratitis progression.

Quercetin is a natural compound with potent antiviral effects; however, its role in the treatment of herpes simplex keratitis (HSK) remains underexplored. Here, we investigated the antiviral effects of quercetin against herpes simplex virus 1 (HSV-1). By examining different phases of viral infection in human corneal epithelial cells (HCECs), we found that 30 μmol/L quercetin inhibits HSV-1 replication primarily by disrupting viral attachment. RNA-sequencing and subsequent analyses revealed that the nuclear factor E2-related factor 2 (Nrf2) was upregulated by quercetin in a dose-dependent manner. Knocking down Nrf2 partially compromised quercetin's antiviral effect. Importantly, topical application of 100 μmol/L quercetin alleviated HSK severity in mice, reduced viral titers in tears, and inhibited VP16 expression in the cornea and trigeminal ganglia. These findings demonstrate the antiviral effect of quercetin against HSV-1 and provide a foundation for mechanistic studies to elucidate its therapeutic potential in HSK.