Inhibitory effect of cycloSaligenyl-nucleoside monophosphates (cycloSal-NMP) of acyclic nucleoside analogues on HSV-1 and EBV

The in vitro antiviral activity of a new series of cycloSal-pro-nucleotides derived from the acyclic nucleoside analogues aciclovir and penciclovir ag ainst herpes simplex virus type 1 (HSV-1), thymidine kinase deficient (TK-) HSV-1, and Epstein-Barr virus (EBV) was evaluated. Using the XTT-based tet razolium reduction assay EZ4U, the cycloSal derivatives were examined for t heir antiviral and cytotoxic,effects in HSV-I as well as HSV-1-TK--infected Vero cells. The anti-EBV activity was assessed by means of an EBV DNA hybr idization assay using a digoxigenin-labaled probe specific for the Barn H1- W-fragment of the EBV genome and by measuring viral capsid antigen (VCA) ex pression in P3HR-1 cells by indirect immunofluorescence. Among the new cycl oSal-phosphotriesters the three aciclovir monophosphates proved to be poten t and selective inhibitors of HSV-I replication, EBV DNA synthesis and EB-V CA expression. Of interest is the retention of activity of the aciclovir mo nophosphates in HSV-1-TK--infected cells. Particularly 3-methyl-cycloSal-ac iclovir monophosphate retained the same effectiveness, as compared to the w ild type virus strain. In contrast to the aciclovir pro-nucleotides the pen ciclovir cyclo Sal-phosphotriesters exhibited at best only a marginal antiv iral effect on HSV and EBV replication. (C) 2000 Elsevier Science B.V. All rights reserved.