Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphonoacetate is a highly specific inhibitor of herpes simplex virus-induced DNA polymerase. Sensitivity of herpesvirus type 1 or type 2 induced DNA polymerase to the drug was similar. However, DNA polymerases from other sources such as the host cells (Wi-38), Micrococcus luteus, and hepatitis B virus were highly resistant. In addition, Escherichia coli RNA polymerase and reverse transcriptase of Rous sarcoma virus were also insensitive to the drug. Enzyme kinetic studies showed that inhibition was noncompetitive with respect to deoxyribonucleotide triphosphates. The Ki value was about 0.45 muM. The apparent Km values for dTTP, dATP, dCTP, and dGTP were 0.71, 0.75, 0.42, and 0.39 muM, respectively. The base composition of template has no profound effect on the extent of inhibition. The drug caused uncompetititve inhibition with respect to template which indicated that phosphonoacetate did not bind directly to template DNA. Results are presented which suggest that phosphonoacetate did not affect the formation of the enzyme-DNA complex but probably inhibited the elongation step of DNA polymerase reaction.
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PMID:Mode of inhibition of herpes simplex virus DNA polymerase by phosphonoacetate. 5 71

Hepatitis B core antibody was detected by radioimmunoprecipitation test using core antigen radiolabelled with 3H-TTP. Core antigen was prepared from Dane particles isolated from plasma of asymptomatic carriers of HbSAg. Sera samples from 286 blood donors found to be HBsAg negative by RIA, 31 patients with chronic hepatitis HBsAg negative and 12 subjects with a past history of acute viral hepatitis B who became HBsAg negative since 2 to 5 years, were tested for anti-HBc and anti-HBs presence. Co-existence of anti-HBc and anti-HBs was found in 32.8% blood donors, 29% chronic hepatitis patients and in all subjects with a past history of disease. Moreover an average of 8.4% of blood donors and 6.4% of chronic hepatitis patients were anti-HBc positive in absence of anti-HBs. The possible significance of anti-HBc as a useful tool for epidemiologic studies is discussed.
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PMID:[Anti-core antibody in HBsAg negative subjects]. 55 42

Hepatitis B core antigen (HBcAg) particles, approximately 27-28 nm in diameter and rho = 1.30-1.35 g/cm3, were purified from the liver of a chimpanzee experimentally infected with hepatitis B virus (HBV) while under cyclophosphamide treatment. The purified HBcAg particles incorporated radioactive deoxythymidine triphosphate. The product was precipitable by trichloroacetic acid and sensitive to DNase, but resistant to digestion by RNase. The reaction required four deoxyribonucleosise triphosphates- dATP, dCTP, dGTP and dTTP. Exogenous template did not enhance the reaction. From these findings, it was suggested that HBcAg particles purified from the HBV-infected chimpanzee liver contained DNA polymerase and endogenous DNA.
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PMID:Hepatitis B core particles with endogenous DNA polymerase activity from chimpanzee liver. 68 Nov 46

Catechin derivatives including (-)-epicatechin gallate (ECG), (-)-epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC) and green tea extract (GTE) were found to inhibit the activities of cloned human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT), duck hepatitis B virus replication complexes reverse transcriptase (DHBV RCs RT), herpes simplex virus 1 DNA polymerase (HSV-1 DNAP) and cow thymus DNA polymerase alpha (CT DNAP alpha). EGCG and ECG were shown to be very potent inhibitors of HIV-1 RT. According to the IC50 values for HIV-1 RT, these compounds can be ordered as EGCG 0.0066 mumol/L > ECG 0.084 mumol/L > GTE 0.1 microgram/ml > EGC 7.2 mumol/L. DHBV RCs RT was the least sensitive to these compounds. Kinetic study showed that EGCG exerts a mixed inhibition with respect to external template inducer poly (rA).oligo (dT) 12-18 and a noncompetitive inhibition with respect to substrate dTTP for HIV-1 RT. Bovine serum albumin significantly reduced the inhibitory effects of catechin analogues and GTE on HIV-1 RT. In tissue culture GTE inhibited the cytopathic effect of coxsackie B3 virus, but did not inhibit the cytopathic effects of HSV-1, HSV-2, influenza A or influenza B viruses.
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PMID:[The inhibitory effects of catechin derivatives on the activities of human immunodeficiency virus reverse transcriptase and DNA polymerases]. 128 89

As the polymerase chain reaction (PCR) can be used for the generation of vector-free probes, the optimum conditions for incorporation of digoxigenin-11-dUTP into hepatitis B virus (HBV) probes have been investigated. High yields of double-stranded or single-stranded probes can be obtained by utilizing a pair of primers or one primer alone. The probes were tested by dot-blot hybridization on HBV plasmid DNA, slot-blot hybridization on total cellular RNA of Alexander cells and Southern blot hybridization on cellular DNA of Alexander cells and HBV plasmid DNA. They were also tested by in situ hybridization (ISH) on HBV-positive biopsy liver tissue. A ratio of dig-dUTP:dTTP of 1:3 gave highest sensitivity in DNA hybridization. No loss of amplification efficiency and sensitivity was observed when the final concentration of dig-11-dUTP and dTTP was reduced to 20 microM and 60 microM respectively, compared to 200 microM each of dATP, dCTP, dGTP. Several different sizes of double-strand probes were compared by dot-blot hybridization. Longer probes were more sensitive. Strong signal could also be obtained by combination of two or three small probes, which have overlapping sequences. Single-stranded DNA probes had advantages of simplicity of use, high sensitivity and strand specificity.
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PMID:Generation of digoxigenin-labelled double-stranded and single-stranded probes using the polymerase chain reaction. 140 27

The 3'-fluoromodified nucleotide analogs 3'-fluorothymidine triphosphate (FdTTP), 2',3'-dideoxy-3'-fluoro-5-chlorouridine triphosphate (F-5CldUTP), 2',3'-dideoxy-3'-fluoro-5-ethyluridine triphosphate (F-5EtdUTP), 2',3'-dideoxy-3'-fluorouridine triphosphate (FdUTP), and 2',3'-dideoxy-3'-fluoro-5-fluorouridine triphosphate (F-5FdUTP) as well as 2',3'-dideoxythymidine triphosphate (ddTTP), 2',3'-didehydro-2',3'-dideoxythymidine triphosphate (ddeTTP), 3'-chlorothymidine triphosphate (CldTTP), and 3'-rhodanothymidine triphosphate (SCNdTTP) were tested for their ability to inhibit hepatitis B virus (HBV)-associated DNA polymerase activity in vitro. The ID50 values of the most potent inhibitors were 0.15 microM for FdTTP, 0.2 microM for ddeTTP, 0.45 microM for ddTTP, and 0.8 microM for F-5CldUTP. SCNdTTP, CldTTP, and F-5EtdUTP were less efficient (ID50 = 3-5 microM), and FdUTP and F-5FdUTP were the least efficient inhibitors (ID50 = 25 microM) of the enzyme activity. Kinetic analysis revealed a competitive type of inhibition for FdTTP and ddeTTP. The Ki values were estimated to be 0.04 microM and 0.08 microM, respectively, compared with a Km value for dTTP of about 0.18 microM.
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PMID:Inhibition of hepatitis B virus DNA polymerase by 3'-fluorothymidine triphosphate and other modified nucleoside triphosphate analogs. 231 73

The duck hepatitis B virus (DHBV)-associated activities of reverse transcriptase and DNA polymerase and their inhibition in vitro were studied. Replicative complexes (RCs) were isolated from DHBV-infected liver by gel chromatography followed by sucrose gradient centrifugation. The RCs were detected by dot blot hybridization, using radiolabeled cloned DHBV DNA as a probe, and by the incorporation of 32P-TTP in the presence of dATP, dCTP, dGTP, and Mg2+ (endogenous DNA polymerase activity). The endogenous DNA polymerase activity associated with RCs was further studied using exogenous templates: reverse transcriptase and DNA polymerase activities were demonstrated using as substrates 32P-TTP and poly(rA) p(dT)12 or poly(dA) p(dT)12-18, respectively. Both activities were biochemically characterized. Their inhibition by various antiviral agents was studied in vitro: actinomycin D, ara-ATP, aphidicolin, suramin, chloroquin, and phosphonoformate. Among these, suramin, chloroquin, phosphonoformate, and ara-ATP were shown to be potent inhibitors of viral reverse transcriptase and DNA polymerase. Studies are now in progress to establish their antiviral activity in vivo.
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PMID:Duck hepatitis B virus: DNA polymerase and reverse transcriptase activities of replicative complexes isolated from liver and their inhibition in vitro. 245 18

Human hepatitis B virus (HBV) DNA polymerase activity was inhibited by pyridoxal 5'-phosphate (PLP) specifically and noncompetitively with respect to deoxythymidine triphosphate (DTTP). NaBH4 reduction of PLP-HBV core proteins resulted in the complete inactivation of HBV DNA polymerase, and PLP modification of the enzyme was though to be mediated through Schiff-base formation. HBV DNA polymerase has a Michaelis constant (Km) of 0.31 microM for dTTP and an apparent inhibition constant (Ki) of 0.2 mM for PLP. Its inactivation and modification by PLP may be useful in the study of not only the reaction mechanism of catalysis, but also the physicochemical nature of the enzyme.
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PMID:Inactivation of human hepatitis B virus DNA polymerase by pyridoxal 5'-phosphate. 272 16

An inhibitory effect of 3'-azido-3'-deoxythymidine triphosphate on hepatitis B virus DNA polymerase was found. No effect was seen by its threo analog. The effect was detected at and above a concentration of 0.05 microM. The inhibition of DNA polymerase activity was the same in ten different strains of HBV. The mechanism was shown to be competitive, with an inhibition constant (Ki) of approximately 0.04 microM, and the Km value for dTTP was 0.1 microM.
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PMID:Inhibition of hepatitis B virus DNA polymerase by 3'-azido-3'-deoxythymidine triphosphate but not by its threo analog. 347 86

A DNA polymerase is associated with the core of the so-called Dane particles. The probability that this is the hepatitis B viral DNA polymerase offers the possibility of preventing hepatitis B multiplication by selective inhibition of this enzyme. We have previously reported that trisodium phosphonoformate (PFA) inhibits Dane particle DNA polymerase. Fifteen compounds with structural similarity to PFA and pyrophosphate have now been tested for inhibition of hepatitis B virus DNA polymerase in an attempt to define the structural requirement for the inhibition. Active structures have two acid groups at close proximity of which at least one is a phosphono group. Phosphonoformate and hypophosphare were the two most active inhibitors. The Ki value for PFA was 7.2 microM when dTTP was used as variable substrate, and the mechanism of inhibition was non-competitive. Phosphonoformate caused rapid shut-off of the polymerase reaction, indicating that it might inhibit elongation. The efficient inhibition of hepatitis B virus DNA polymerase by PFA and its low toxicity suggest that it could be used to inhibit hepatitis B virus multiplication in vivo.
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PMID:Inhibition of hepatitis B Dane particle DNA polymerase activity by pyrophosphate analogs. 625 41


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