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Inhibitory effect of cycloSaligenyl-nucleoside monophosphates (cycloSal-NMP) of acyclic nucleoside analogues on HSV-1 and EBV. 2000

A Meerbach, and R Klöcking, and C Meier, and A Lomp, and B Helbig, and P Wutzler
Institute for Antiviral Chemotherapy, Friedrich-Schiller-University Jena, Erfurt, Germany. meerbach@zmkh.ef.uni-jena.de

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.

UI MeSH Term Description Entries
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002522 Chlorocebus aethiops A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research. African Green Monkey,Cercopithecus aethiops,Cercopithecus griseoviridis,Cercopithecus griseus,Cercopithecus pygerythrus,Cercopithecus sabeus,Cercopithecus tantalus,Chlorocebus cynosuros,Chlorocebus cynosurus,Chlorocebus pygerythrus,Green Monkey,Grivet Monkey,Lasiopyga weidholzi,Malbrouck,Malbrouck Monkey,Monkey, African Green,Monkey, Green,Monkey, Grivet,Monkey, Vervet,Savanah Monkey,Vervet Monkey,Savannah Monkey,African Green Monkey,Chlorocebus cynosuro,Green Monkey, African,Green Monkeys,Grivet Monkeys,Malbrouck Monkeys,Malbroucks,Monkey, Malbrouck,Monkey, Savanah,Monkey, Savannah,Savannah Monkeys,Vervet Monkeys
D004279 DNA, Viral Deoxyribonucleic acid that makes up the genetic material of viruses. Viral DNA
D004854 Herpesvirus 4, Human The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies. Burkitt Herpesvirus,Burkitt Lymphoma Virus,E-B Virus,EBV,Epstein-Barr Virus,Human Herpesvirus 4,Infectious Mononucleosis Virus,Burkitt's Lymphoma Virus,HHV-4,Herpesvirus 4 (gamma), Human,Burkitts Lymphoma Virus,E B Virus,E-B Viruses,Epstein Barr Virus,Herpesvirus, Burkitt,Infectious Mononucleosis Viruses,Lymphoma Virus, Burkitt,Mononucleosis Virus, Infectious,Mononucleosis Viruses, Infectious
D006147 Guanine
D000212 Acyclovir A GUANOSINE analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Acycloguanosine,9-((2-Hydroxyethoxy)methyl)guanine,Aci-Sanorania,Acic,Aciclobeta,Aciclostad,Aciclovir,Aciclovir Alonga,Aciclovir-Sanorania,Acifur,Acipen Solutab,Acivir,Activir,Acyclo-V,Acyclovir Sodium,Antiherpes Creme,Avirax,Cicloferon,Clonorax,Cusiviral,Genvir,Herpetad,Herpofug,Herpotern,Herpoviric,Isavir,Laciken,Mapox,Maynar,Milavir,Opthavir,Supraviran,Viclovir,Vipral,Virax-Puren,Virherpes,Virmen,Virolex,Virupos,Virzin,Wellcome-248U,Zoliparin,Zovirax,Zyclir,aciclovir von ct,Aci Sanorania,Aciclovir Sanorania,Acyclo V,Alonga, Aciclovir,Sodium, Acyclovir,Solutab, Acipen,Virax Puren,ViraxPuren,Wellcome 248U,Wellcome248U
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000956 Antigens, Viral Substances elaborated by viruses that have antigenic activity. Viral Antigen,Viral Antigens,Antigen, Viral
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D013937 Thymidine Kinase An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. Deoxythymidine Kinase,Deoxypyrimidine Kinase,Kinase, Deoxypyrimidine,Kinase, Deoxythymidine,Kinase, Thymidine

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