Effect of A-5021 on Experimental Herpetic Keratitis

Abstract

Abstract: : Purpose: (1’S,2’R)-9-{[1’,2’-Bis(hydroxymethyl)cycloprop-1’-yl]methyl} guanine (A-5021) is efficacious in the treatment of intraperitoneal, cutaneous, and encephalitic herpes simplex virus type 1 (HSV-1) infection but has not been used to treat ocular HSV-1 infections. We investigated antiherpetic activity of topical A-5021 on herpetic keratitis. Methods: BALB/c mice were inoculated with HSV-1 strain CHR 3 and treated three times with increasing concentrations of A-5021 eye drop (0.025 to 0.20%). The keratitis scores and infectious viral titers in eye balls and trigeminal ganglia (TGs) were examined (Experiment 1). The efficacy of 0.1% A-5021 was also compared to topical treatment with 3% acyclovir (ACV) ointment (Experiment 2). Results: 0.05, 0.10, and 0.20% A-5021 was effective on herpetic epithelial keratitis in slit lamp examination scores. All the concentrations examined of A-5021 also resulted in improvement of stromal keratitis. However, there was no significant difference in the amounts of infectious virus present in the eye balls and TG of mice in the A-5021 groups compared to those in the placebo group (Experiment 1). Topical 0.1% A-5021 treatment was effective as 3% ACV at reducing epithelial and stromal lesions. The infectious virus in TG was not detected in ACV group, but detected in A-5021 group (Experiment 2). Conclusions: Topical A-5021 treatment significantly reduces the severity of herpetic epithelial and stromal keratitis. However, A-5021 may not be so effective about reducing the establishment of latency as ACV.

Keywords: herpes simplex virus • antiviral drugs • animal model