Evaluating the therapeutic efficacy of triptolide and (S)-10-hydroxycamptothecin on cutaneous and ocular Herpes Simplex Virus type-1 infections in mice

OBJECTIVE: The emergence of Acyclovir-Resistant Herpes Simplex Virus type-1, which is the result of clinical over usage calls for the urgent need of a novel anti-HSV agent. Hence, the activity of Triptolide (TP) and (S)-10-Hydroxycamptothecin (10-HCPT) were investigated as natural products in two infection models of HSV-1. METHODS: The antiviral efficacy of TP and 10-HCPT was evaluated in mice ocular and cutaneous infection models of HSV. Groups of 10 mice were infected with HSV-1. Both compounds were administered topically on corneal and skin. The disease severity, viral titer (plaque reduction assay), and histopathology were evaluated in the ocular and cutaneous models of HSV-1 infection on days 3, 5, 7, 9, and 12 post infection, as well as genome loads on days 3 and 12. RESULTS: Topical treatment of corneal with TP, 10-HCPT, and ACV was effective in reducing stromal disease (after day 3, P = 0.001), plus TP and ACV on vascularization (after day 7, P = 0.001). The virus titer decreased significantly in the infected treated groups after day 3 (P < 0.05). Also, on day 12 post-infection, the virus genome volume in the TP and ACV groups was significantly reduced. With respect to virus titers and the DNA yield, significant difference was observed, merely in the ACV group in comparison to the control (P = 0.013). Immunohistochemistry analysis showed that corneal epithelium healing was partially visible in the 10-HCPT group, which gradually increased in TP, and was the highest in the ACV group. The skin epithelium healing was only observed in TP and ACV groups, and was superior in the ACV group. CONCLUSIONS: This study revealed the virologic and clinical potential of TP in-vivo to treat ocular mouse model.