The Effect of High-Dose, Short-Term Amenamevir Therapy before Skin Lesion Onset in a Mouse Model of Cutaneous Herpes Simplex Virus Type 1 Infection

This is the authors' abstract. We don't add key points for this paper.

Amenamevir (AMNV) is a helicase-primase inhibitor antiviral drug used to treat herpes simplex infections, such as herpes labialis and genital herpes, which are caused by reactivation of latent herpes simplex virus (HSV) in the dorsal root ganglia (DRG). Patient-initiated therapy (PIT), in which patients self-administer high-dose antiviral drugs for a short term before rash onset, is a useful treatment strategy for recurrent herpes labialis and genital herpes. However, the efficacy of AMNV administered as PIT on HSV viral loads in the DRG remains unclear. In this study, we investigated the effects of high-dose, short-term AMNV therapy on skin lesions and viral loads in the DRG using a mouse model of cutaneous HSV type 1 infection. HSV type 1 was percutaneously inoculated into the femoral region of mice. AMNV was orally administered either once daily for 2 d before rash onset or twice daily for 5 d after onset. Vidarabine was topically administered twice daily for 5 d after rash onset. Viral load in the DRG was quantified by quantitative PCR. High-dose, short-term AMNV therapy administered before rash onset significantly inhibited the development of skin lesions and reduced viral load compared with low-dose, long-term AMNV therapy and topical vidarabine treatment administered after onset. These results demonstrate that high-dose, short-term AMNV therapy administered before rash onset was associated with reduced viral load in the DRG and suppression of skin lesion development, supporting the need for early intervention with adequate antiviral exposure.