Host-directed novel mechanistic insights of doxorubicin reveal its efficacy against drug-resistant HSV-1 underscoring risks with oncolytic virotherapy

This study identifies PI3K-AKT pathway inhibition as a novel host-directed antiviral mechanism underlying doxorubicin's activity against HSV-1, demonstrates its synergistic potential with nucleoside analogs, and provides mechanistic insight into raising concerns over oncolytic HSV-based therapies. Collectively, these findings highlight the potential of localized, host-targeted strategies for managing drug-resistant HSV-1 infections.