Biomaterial Database

Inhibitory efficacy of cyclosal-nucleoside monophosphates of aciclovir and brivudin on DNA synthesis of orthopoxvi ruses. 2006

Andreas Sauerbrei, and Chris Meier, and Astrid Meerbach, and Peter Wutzler

Institute of Virology and Antiviral Therapy, University of Jena, Jena, Germany. Andreas.Sauerbrei@med.uni-jena.de

Previous studies have shown that cycloSaligenyl-monophosphate (cycloSal-MP) derivatives of aciclovir (ACV), penciclovir (PCV) and brivudin (BVDU) can act as inhibitors of vaccinia virus and cowpox virus replication in vitro. The aim of the present study was to evaluate the inhibatory efficacy on DNA synthesis in vaccinia and cowpox viruses of several cycloSal-pro-nucleotides of ACV and BVDU, which have proven activity against pox viruses. Viral DNA was quantified in treated and non-treated virus-infected cells by semi-quantitative PCR on the basis of the haemagglutinin protein gene of orthopoxviruses. As result, an inhibitory efficacy on vaccinia and cowpox virus DNA replication could be demonstrated for 3-methyl-cycloSal-ACVMP, 5-H-cycloSal-ACVMP, 6-chloro-7-ECM-cycloSal-3'-OH-BVDUMP, and 6-chloro-7-methyl-cycloSal-3'-OH-BVDUMP. At concentrations of 32-128 mg/ml, 3-methyl-cyc/oSal-ACVMP and 6-chloro-7-ECM-cycloSal-3'OH-BVDUMP inhibited synthesis of viral DNA to a similar extent as the well-known inhibitors of pox viruses, cidofovir and 5-iodo-dUrd (deoxyuridine). When concentrations of 128 mg/ml were administered, both test substances diminished the amount of viral genome copies by > or =4 log10 corresponding to > or =99.99% reduction. In conclusion, selected cycloSal-pro-nucleotide derivatives of ACV and BVDU can inhibit orthopoxviral DNA synthesis. The high inhibitory efficacy on both replication of viral DNA and infectious viral particles in cell cultures makes these compounds promising candidates for in vivo experiments.

UI	MeSH Term	Description	Entries
D011213	Poxviridae Infections	Virus diseases caused by the POXVIRIDAE.	Milker's Nodes,Orthopoxvirus Infection,Poxvirus Infections,Infections, Poxviridae,Infections, Poxvirus,Infection, Orthopoxvirus,Infection, Poxviridae,Infection, Poxvirus,Milker Nodes,Milker's Node,Milkers Nodes,Orthopoxvirus Infections,Poxviridae Infection,Poxvirus Infection
D001973	Bromodeoxyuridine	A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.	BUdR,BrdU,Bromouracil Deoxyriboside,Broxuridine,5-Bromo-2'-deoxyuridine,5-Bromodeoxyuridine,NSC-38297,5 Bromo 2' deoxyuridine,5 Bromodeoxyuridine,Deoxyriboside, Bromouracil
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
D004261	DNA Replication	The process by which a DNA molecule is duplicated.	Autonomous Replication,Replication, Autonomous,Autonomous Replications,DNA Replications,Replication, DNA,Replications, Autonomous,Replications, DNA
D004279	DNA, Viral	Deoxyribonucleic acid that makes up the genetic material of viruses.	Viral DNA
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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
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
D014709	Vero Cells	A CELL LINE derived from the kidney of the African green (vervet) monkey, (CHLOROCEBUS AETHIOPS) used primarily in virus replication studies and plaque assays.	Cell, Vero,Cells, Vero,Vero Cell