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)

The effect of analogues of both 2',3'-dideoxy-3'-fluorothymidine (FddThd) [2',3'-dideoxy-3'-fluorouridine (FddUrd), 2',3'-dideoxy-3'-fluoro-5-chlorouridine (FddClUrd), 2',3'-dideoxy-3'- fluoro-5-bromouridine (FddBrUrd) and 2',3'-dideoxy-3'-fluoro-5-bromovinyluridine (FddBVUrd)] and 2',3'-dideoxy-3'-fluorocytidine (FddCyt) [2',3'-dideoxy-3'-fluoro-5-fluorocytidine (FddFCyt), 2',3'-dideoxy-3'-fluoro-5-chlorocytidine (FddClCyt), 2',3'-dideoxy-3'-fluoro-5-methylcytidine (FddMeCyt), 2',3'-dideoxy-3'-fluoro-5-ethylcytidine (FddEtCyt), 2',3'-dideoxy-3'-chloro-5-methylcytidine (ClddMeCyt), 2',3'-dideoxy-3'-amino-5-methylcytidine (AmddMeCyt), 2',3'-dideoxy-3'-azido-5- methylcytidine (AzddMeCyt) and arabinosyl-5-methylcytosine (AraMeCyt)] were tested for their potential antiviral activity in vitro using the human hepatoblastoma cell line, Hep G2 2.2.15, which was transfected with a vector containing hepatitis B virus (HBV). It was found that FddThd, FddMeCyt, FddEtCyt, ClddMeCyt, AmddMeCyt and AraMeCyt display cytostatic activity at concentrations (CD50 values) between 0.54 (FddMeCyt) and 3.93 microM (FddEtCyt), while FddUrd, FddClUrd, FddBrUrd, FddBVUrd, FddCyt, FddFCyt, FddClCyt and AzddMeCyt do not affect cell growth at concentrations of up to 25 microM. Among the thymidine analogues tested, FddThd is the most effective antiviral agent: at a concentration of 0.03 microM a more than 90% reduction of HBV DNA synthesis was measured. On the other hand, the antiviral indexes displayed by FddClUrd, FddBrUrd and FddBVUrd are higher than tht of FddThd; FddUrd was completely inactive. The most powerful antiviral agents in the group of cytidine analogues tested in vitro were FddMeCyt (more than 90% reduction of HBVDNA synthesis at 0.10 microM) and ClddMeCyt (0.10 microM); FddClCyt, FddEtCyt, AmddMeCyt and AraMeCyt were of intermediate activity. None of the negligible antiviral activity was determined for FddUrd, FddCyt, FddFCyt and AzddMeCyt. FddThd and FddMeCyt displayed in vivo an antiviral effect in the duck/duck HBV (DHBV) animal system. Administration of 10 or 20 mg/kg (total daily dose) of FddThd and 5 or 10 mg/kg of FddMeCyt (i.m. daily) to ducks infected with DHBV for 12 days blocked virus production. Termination of treatment with FddThd of infected animals led to reappearance of the virus in the serum though at lower levels. The in vitro and the in vivo data suggest that FddThd and FddMeCyt might be promising antiviral agents for the treatment of infection caused by HBV in humans.
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PMID:Inhibition of hepatitis B virus production by modified 2',3'-dideoxy-thymidine and 2',3'-dideoxy-5-methylcytidine derivatives. In vitro and in vivo studies. 131 7

The process conditions for recombinant hepatitis B surface antigen (HBsAg) extraction from transgenic potato were examined. The effects of temperature, the reducing agent beta-mercaptoethanol (BME), and proteinase inhibitors on the level of antigenic activity of recovered HBsAg were determined. Sedimentation profiles were performed to characterize HBsAg assembly into virus-like particles. Increasing the temperature of the sample for about 1 min increased the measured HBsAg antigenic activity. The optimum temperature was around 50 degrees C. A 3-fold enhancement of the antigenic activity was obtained in extract from transgenic potato expressing HBsAg, when monoclonal antibodies were used to assay for HBsAg. When antigenic activity was determined by polyclonal antibodies, no enhancement in the antigenic activity was obtained. Temperature may affect the conformation of the a epitope to which the monoclonal antibodies bind or alter the fluidity of surface lipid regions. BME increased the antigenic activity of HBsAg up to 4-fold when monoclonal antibodies directed against the a determinant were used, but there was no increase with polyclonal antibodies. This observation suggests that BME affects the structure or presentation of the a epitope. In the presence of BME and leupeptin, a proteinase inhibitor, higher antigenic activity was obtained. Leupeptin might protect the antigen, which might become more susceptible to proteolytic degradation after reduction, as a result of stimulation of sulfhydryl proteases. Although both temperature and BME increased the antigenic activity of HBsAg individually, when combined their interaction was antagonistic, resulting in reduced antigenic activity. Different proteinase inhibitors, including leupeptin, aprotinin, E-64, pefabloc, and pepstatin, had no significant effect on HBsAg from potato extract in a 2 h period in the absence of BME. The sedimentation profile of potato-produced HBsAg was determined in 5-30% sucrose gradients. Yeast-derived recombinant HBsAg was used as a positive control. The HBsAg from transgenic potato showed sedimentation and density properties that are very similar to the yeast-produced antigen, indicating assembly into virus-like particles. BME treatment did not change the sedimentation profile.
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PMID:Process options in hepatitis B surface antigen extraction from transgenic potato. 1083 46