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 against herpes simplex virus type 1 (HSV-1), thymidine kinase deficient (TK-) HSV-1, and Epstein-Barr virus (EBV) was evaluated. Using the XTT-based tetrazolium reduction assay EZ4U, the cycloSal derivatives were examined for their antiviral and cytotoxic effects in HSV-1 as well as HSV-1-TK--infected Vero cells. The anti-EBV activity was assessed by means of an EBV DNA hybridization assay using a digoxigenin-labeled probe specific for the Bam H1-W-fragment of the EBV genome and by measuring viral capsid antigen (VCA) expression in P3HR-1 cells by indirect immunofluorescence. Among the new cycloSal-phosphotriesters the three aciclovir monophosphates proved to be potent and selective inhibitors of HSV-1 replication, EBV DNA synthesis and EB-VCA expression. Of interest is the retention of activity of the aciclovir monophosphates in HSV-1-TK--infected cells. Particularly 3-methyl-cycloSal-aciclovir monophosphate retained the same effectiveness, as compared to the wild type virus strain. In contrast to the aciclovir pro-nucleotides the penciclovir cycloSal-phosphotriesters exhibited at best only a marginal antiviral effect on HSV and EBV replication.
Meerbach
A
A
Institute for Antiviral Chemotherapy, Friedrich-Schiller-University Jena, Erfurt, Germany. meerbach@zmkh.ef.uni-jena.de
Klöcking
R
R
Meier
C
C
Lomp
A
A
Helbig
B
B
Wutzler
P
P
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D036022:Capsid Proteins; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000096:biosynthesis; D006147:Guanine; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D000956:Antigens, Viral; D000998:Antiviral Agents; D036022:Capsid Proteins; D004279:DNA, Viral; C041788:Epstein-Barr viral capsid antigen; C053539:penciclovir; D006147:Guanine; D013937:Thymidine Kinase; D000212:Acyclovir