Novel Hsp90 inhibitor JD‑02 inhibits HSV‑1 infection via the Raf/MEK/ERK signaling pathway.

Herpes simplex virus type 1 (HSV‑1) is a neurotropic pathogen with an extremely high infection rate. The excessive use of acyclovir (ACV) and nucleoside analogs has resulted in the emergence of drug‑resistant HSV‑1 strains, thereby underscoring the need for the development of novel therapeutic agents against HSV‑1. The present study sought to evaluate the efficacy and elucidate the mechanism of action of the novel Hsp90 inhibitor, JD‑02, in the context of HSV‑1 infection, as well as to assess its potential as an anti‑HSV‑1 therapeutic agent. The results of the present study demonstrated that JD‑02 exhibits lower cytotoxicity relative to the conventional Hsp90 inhibitor, AT533, and effectively inhibits infection by both standard and ACV‑resistant HSV‑1 strains in vitro. Additionally, JD‑02 markedly suppresses the expression of viral‑associated genes and proteins. The present investigation further revealed that the Raf/MEK/ERK signaling pathway is activated during HSV‑1 infection, and that JD‑02 exerts its antiviral effects through the inhibition of this pathway. Moreover, the in vivo administration of JD‑02 mitigated the symptoms of Herpes simplex encephalitis (HSE), extended the lifespan of mice with HSE, and decreased both the viral gene copy number and the expression of inflammatory factors. In contrast to targeting viral DNA polymerases, Hsp90 inhibitors, which target host proteins, exhibit a significantly lower likelihood of inducing drug resistance. These findings indicate that JD‑02, a novel HSP90 inhibitor, holds promise for development as a therapeutic agent for the treatment of HSV‑1 infection and associated diseases.