A stapled viral peptide blocks HSV-2 from infecting human cervical cells

Herpes Simplex Virus-2 (HSV-2) is the leading cause of genital herpes. Currently, no vaccines are available to prevent HSV-2 infection. Moreover, resistance to acyclovir, a commonly used drug to treat HSV-2 infection, is a growing concern. Herein, we show that the stapled peptide SPep7B, originally developed as a potential antiviral against HSV-1 for treating human herpes ocular keratitis, has the extended ability to target HSV-2 replication in vitro and block HSV-2 infection in three-dimensional (3D) human vaginal cells. We also demonstrate that SPep7B exhibits low cytotoxicity, non-mutagenicity, remarkable metabolic stability in plasma, and the ability to penetrate epithelial tissue. Together, these findings support the potential of SPep7B as a topical treatment for HSV-2 genital herpes.