Treatment with meliacine, a plant derived antiviral, prevents the development of herpetic stromal keratitis in mice

Herpetic stromal keratitis is caused by ocular infection with herpes simple x virus type 1 (HSV-1) and constitutes a leading cause of human blindness. The effect of meliacine, an antiviral compound isolated from leaves of Meli a azedarach L. that inhibits HSV-1 replication in vitro, was examined on ex perimental corneal HSV-1 inoculation in Balb/c mice. Mice were inoculated w ith HSV-1 strain KOS at their corneas after abrasion. Meliacine was adminis tered topically 3 times a day for 4 days beginning 1 day before inoculation . Infected animals treated or not with meliacine were observed carefully fo r the development of stromal keratitis and the clinical scoring was done 14 days post-infection. Histological examination of corneas and viral isolati on from eyes from HSV-1 infected mice treated or not with meliacine were al so carried out. It was found that the treatment of HSV-1-induced ocular dis ease in Balb/c mice with meliacine reduced significantly the development of clinical disease, as well as the histological damage in corneas. The viral titers detected in eyes of infected and treated mice were 2-orders-of-magn itude lower than those corresponding to HSV-1 infected control animals. Moc k-infected and treated mice did not reveal any corneal alteration due to th e administration of the compound. Meliacine was found to exert a strong ant iviral action on HSV-1-induced ocular disease in mice with no evidence of t oxic effects. J. Med. Virol. 61:474-480, 2000. (C) 2000 Wiley-Liss, Inc.