Biomaterial Database

Inhibition of RNA- and DNA-dependent duck hepatitis B virus DNA polymerase activity by nucleoside and pyrophosphate analogs. 1989

B Löfgren, and E Nordenfelt, and B Oberg

Department of Medical Microbiology, University of Lund, Sweden.

The DNA polymerase of hepadnaviruses has two different functions during virus replication. It acts both as an RNA-dependent DNA polymerase (reverse transcriptase) and as a DNA-dependent DNA polymerase. Duck hepatitis B virus (DHBV) preparations were used to investigate the inhibitory effects of selected compounds on these two enzyme activities. The reverse transcriptase activity was represented by an actinomycin D-resistant, phosphonoformate-sensitive DNA polymerase activity isolated from DHBV-infected duck livers. DHBV from serum was used as the source of the DNA-dependent DNA polymerase activity. Pyrophosphate and nucleoside triphosphate analogs were assayed for their inhibitory effects on the two enzyme preparations. A marked inhibition was obtained with 3'-fluoro-2',3'-dideoxythymidine 5'-triphosphate, acyclovir triphosphate, 2',3'-dideoxythymidine 5'-triphosphate, 2',3'-dideoxyguanosine 5'-triphosphate and 2',3'-dideoxythymidine 5'-triphosphate. The two thymidine analog triphosphates showed a markedly lower inhibitory effect on the reverse transcriptase activity than on the DNA-dependent DNA polymerase activity. This was in analogy with earlier findings with 3'-azido-2',3'-dideoxythymidine 5'-triphosphate. Among the tested pyrophosphate analogs only phosphonoformate was inhibitory.

UI	MeSH Term	Description	Entries
D009711	Nucleotides	The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)	Nucleotide
D010746	Phosphonoacetic Acid	A simple organophosphorus compound that inhibits DNA polymerase, especially in viruses and is used as an antiviral agent.	Phosphonoacetate,Disodium Phosphonoacetate,Fosfonet Sodium,Phosphonacetic Acid,Phosphonoacetate, Disodium
D011756	Diphosphates	Inorganic salts of phosphoric acid that contain two phosphate groups.	Diphosphate,Pyrophosphate Analog,Pyrophosphates,Pyrophosphate Analogs,Analog, Pyrophosphate
D002642	Chick Embryo	The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.	Embryo, Chick,Chick Embryos,Embryos, Chick
D004259	DNA-Directed DNA Polymerase	DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair.	DNA Polymerase,DNA Polymerases,DNA-Dependent DNA Polymerases,DNA Polymerase N3,DNA Dependent DNA Polymerases,DNA Directed DNA Polymerase,DNA Polymerase, DNA-Directed,DNA Polymerases, DNA-Dependent,Polymerase N3, DNA,Polymerase, DNA,Polymerase, DNA-Directed DNA,Polymerases, DNA,Polymerases, DNA-Dependent DNA
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
D012194	RNA-Directed DNA Polymerase	An enzyme that synthesizes DNA on an RNA template. It is encoded by the pol gene of retroviruses and by certain retrovirus-like elements. EC 2.7.7.49.	DNA Polymerase, RNA-Directed,RNA-Dependent DNA Polymerase,Reverse Transcriptase,RNA Transcriptase,Revertase,DNA Polymerase, RNA Directed,DNA Polymerase, RNA-Dependent,RNA Dependent DNA Polymerase,RNA Directed DNA Polymerase
D015611	Hepatitis B Virus, Duck	A DNA virus that closely resembles human hepatitis B virus. It has been recovered from naturally infected ducks.	DHBV,Duck hepatitis B virus,Duck Hepatitis B Viruses,Hepatitis B Viruses, Duck
D017245	Foscarnet	An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV.	Phosphonoformate,Phosphonoformic Acid,Foscarnet Barium (2:3) Salt,Foscarnet Calcium (2:3) Salt,Foscarnet Disodium Salt,Foscarnet Magnesium (2:3) Salt,Foscarnet Manganese (2+) (2:3) Salt,Foscarnet Sodium,Foscarnet Sodium Hexahydrate,Foscarnet Trilithium Salt,Foscarnet Tripotassium Salt,Foscarnet Trisodium Salt,Foscavir,Trisodium Phosphonoformate