Antiherpetic Activity of Imiquimod-Based Ruthenium Metal Complexes

The efficacy of nucleoside analogs in treating Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections is often compromised by drug resistance and adverse effects. As an alternative or complementary approach, host-targeting antivirals offer a promising strategy for managing HSV infections. In this context, the immunomodulatory compound Imiquimod and its derivatives have emerged as potential treatments for recurrent HSV infections, with clinical reports highlighting successful outcomes in patients resistant to conventional antiviral therapies. To advance this field, we have developed a library of novel Imiquimod-based ruthenium complexes with potent antiviral properties. Our findings reveal that derivatives RM11, MAF09, and ACC71 exhibit enhanced antiviral efficacy against HSV-1 and HSV-2 in both primary and cancerous cell lines when compared to Imiquimod alone. Moreover, these complexes demonstrate lower cytotoxicity and higher efficacy than the approved organic drug. Overall, our results highlight Imiquimod-based ruthenium metal complexes as promising candidates for developing novel therapeutic strategies against HSV infections.