Antiviral effects of 28-deacetylsendanin on herpes simplex virus-1 replication

The compound purified from the fruit of Melia azedarach exerted an antivira l effect on herpes simplex virus-1 (HSV-I) in Vero cells. It was identified as 28-deacetylsendanin (28-DAS). The 50% inhibitory concentration (IC50) o f 28-DAS was 1.46 mu g/ml without cytotoxicity at 400 mu g/ml on Vero cells . Electron microscopy showed that low electron-dense cores of newly synthes ized nucleocapsids remained in swollen nuclei and no extracellular virus pa rticles were observed at 15 h pi Consistent with this result, it was confir med by a plaque assay that few infectious progeny viruses were released fro m the 28-DAS-treated virus-infected cells at 24 h p.i. Intracellular viruse s in 28-DAS-treated virus-infected cells were 23% of untreated and infected cells. The synthesis of thymidine kinase (TK) was reduced by 28-DAS at ear ly stage. In conclusion, 28-DAS inhibited the replication of HSV-I, reduced the synthesis of HSV-1 TK, and led to the formation of defective nucleocap sids. (C) 1999 Elsevier Science B.V. All rights reserved.