scholarly journals Novel Acyclic Nucleoside Phosphonate Analogues with Potent Anti-Hepatitis B Virus Activities

2005 ◽  
Vol 49 (3) ◽  
pp. 1177-1180 ◽  
Author(s):  
C. Ying ◽  
A. Holý ◽  
D. Hocková ◽  
Z. Havlas ◽  
E. De Clercq ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Amino Group ◽  
Wild Type ◽  
Pyrimidine Base ◽  
B Virus ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside ◽  
Acyclic Nucleoside Phosphonate

ABSTRACT Novel acyclic nucleoside phosphonates with a pyrimidine base preferentially containing an amino group at C-2 and C-4 and a 2-(phosphonomethoxy)ethoxy or (R)-2-(phosphonomethoxy)propoxy group at C-6 selectively inhibit the replication of wild-type and lamivudine-resistant hepatitis B viruses. The activity of the most potent compounds was comparable to that of adefovir.

Inhibitory Effects of Acyclic Nucleoside Phosphonate Analogues on Hepatitis B Virus DNA Synthesis in HB611 Cells

1994 ◽  
Vol 5 (2) ◽  
pp. 57-63 ◽  
Author(s):  
T. Yokota ◽  
K. Konno ◽  
S. Shigeta ◽  
A. Holy ◽  
J. Balzarini ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Dna Synthesis ◽  
Dna Polymerase ◽  
Hbv Dna ◽  
Inhibitory Effects ◽  
B Virus ◽  
Acyclic Nucleoside ◽  
Cellular Dna ◽  
Acyclic Nucleoside Phosphonate

By using an assay system based on a human hepatoblastoma cell line (HB611) that continuously synthesizes hepatitis B virus (HBV) DNA, 56 acyclic nucleoside phosphonate analogues were examined for their inhibitory effects on HBV DNA synthesis. The following compounds were found to inhibit HBV DNA synthesis at concentrations that were significantly lower than their minimum cytotoxic concentrations; 9-(2-phosphonylmethoxyethyl)adenine (PMEA), 9-(2-phosphonylmethoxyethyl) guanine(PMEG), 9-(2-phosphonylmethoxyethyl) guanine ethyl ester (PMEGEE), 9 - (2 - phosphonylmethoxyethyl) - 1 - deazaadenine (PMEC1A), 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP), ( S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA), 9-(3-isopropoxy-2-phosphonylmethoxypropyl)adenine (IPPMPA), 9-( RS)-(2-phosphonylmethoxypropyl)adenine (PMPA) and 9-(3-hydroxy-2-phosphonylmethoxypropyl)-2, 6-diaminopurine (HPMPDAP). The most selective compounds (with indexes greater than 100) were PMEDAP, PMEA, IPPMPA, and PMPA. Acyclic pyrimidine nucleoside phosphonate analogues did not prove markedly selective as anti-HBV agents. Diphosphoryl derivatives of some acyclic purine nucleoside phos-phonates (i.e. PMEA, PMEDAP, HPMPA) were prepared. They proved inhibitory to HBV DNA polymerase but not cellular DNA polymerase α.

scholarly journals Antiviral Activities of Novel 5-Phosphono-Pent-2-en-1-yl Nucleosides and Their Alkoxyalkyl Phosphonoesters

2006 ◽  
Vol 51 (2) ◽  
pp. 611-615 ◽  
Author(s):  
Hyunah Choo ◽  
James R. Beadle ◽  
Earl R. Kern ◽  
Mark N. Prichard ◽  
Kathy A. Keith ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Oral Bioavailability ◽  
Dna Viruses ◽  
B Virus ◽  
Acyclic Nucleoside Phosphonates ◽  
Antiviral Activities ◽  
Acyclic Nucleoside

ABSTRACT Three acyclic nucleoside phosphonates are currently approved for clinical use against infections caused by cytomegalovirus (Vistide), hepatitis B virus (Hepsera), and human immunodeficiency virus type 1 (Viread). This important antiviral class inhibits viral polymerases after cellular uptake and conversion to their diphosphates, bypassing the first phosphorylation, which is required for conventional nucleoside antivirals. Small chemical alterations in the acyclic side chain lead to marked differences in antiviral activity and the spectrum of activity of acyclic nucleoside phosphonates against various classes of viral agents. We synthesized a new class of acyclic nucleoside phosphonates based on a 5-phosphono-pent-2-en-1-yl base motif in which the oxygen heteroatom usually present in acyclic nucleoside phosphonates has been replaced with a double bond. Since the intrinsic phosphonate moiety leads to low oral bioavailability and impaired cellular penetration, we also prepared the hexadecyloxypropyl esters of the 5-phosphono-pent-2-en-1-yl nucleosides. Our earlier work showed that this markedly increases antiviral activity and oral bioavailability. Although the 5-phosphono-pent-2-en-1-yl nucleosides themselves were not active, the hexadecyloxypropyl esters were active against DNA viruses and hepatitis B virus, in vitro. Notably, the hexadecyloxypropyl ester of 9-(5-phosphono-pent-2-en-1-yl)-adenine was active against hepatitis B virus mutants resistant to lamivudine, emtricitabine, and adefovir.

Precore/Core Promoter Mutant Hepatitis B Virus Produces More Severe Histologic Liver Disease than Wild Type Hepatitis B Virus

2007 ◽  
Vol 1 (1) ◽  
pp. 41-46 ◽  
Author(s):  
Mamun-Al-Mahtab ◽  
Salimur Rahman ◽  
Mobin Khan ◽  
Ayub Mamun ◽  
Kamal
Keyword(s):  
Liver Disease ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Promoter ◽  
Wild Type ◽  
B Virus ◽  
Promoter Mutant

scholarly journals Analysis of the complete genome of hepatitis B virus subgenotype C2 isolate NHB17965 from a HBV infected patient

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1023 ◽  
Author(s):  
Modhusudon Shaha ◽  
Palash Kumar Sarker ◽  
Md. Saddam Hossain ◽  
Keshob Chandra Das ◽  
Munira Jahan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Complete Genome ◽  
Infected Patient ◽  
Surface Proteins ◽  
Wild Type ◽  
Small Surface ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Complete Genome Analysis

The burden of chronic hepatitis B virus (HBV) infections is increasingly detected nowadays. Herein, we report a complete genome of HBV subgenotype C2 (HBV/C2) from a HBV infected patient. Complete genome analysis revealed that the isolated strain was a non-recombinant wild type and had several regular substitutions in the reverse transcriptase domain and small surface proteins of HBV. This study may help clinicians and scientists gain in-depth knowledge on the current substitutions of HBV/C2 genome and to identify potential therapies against HBV infections.

scholarly journals Nucleolar Localization of Human Hepatitis B Virus Capsid Protein

2004 ◽  
Vol 78 (24) ◽  
pp. 13653-13668 ◽  
Author(s):  
Bo Ning ◽  
Chiaho Shih
Keyword(s):  
Amino Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Epitope ◽  
Core Antigen ◽  
Wild Type ◽  
Confocal Immunofluorescence Microscopy ◽  
Human Hepatitis ◽  
C Terminus ◽  
B Virus

ABSTRACT Wild-type human hepatitis B virus (HBV) exhibits selective export of virions containing mature genomes. In contrast, changing an isoleucine to a leucine at amino acid 97 (I97L) of the HBV core antigen (HBcAg) causes it to release immature genomes. To elucidate the structure-function relationship of HBcAg at amino acid 97, we systematically replaced the isoleucine residue at this position with 18 other amino acids via mutagenesis. Twelve of the 18 mutants exhibited no significant phenotype, while five new mutants displayed strong phenotypes. The I97D mutant had a near lethal phenotype, the I97P mutant exhibited a significantly reduced level of virion secretion, and the I97G mutant lacked the full-length relaxed circular form of viral DNA. The tip of the spike of the capsid particle is known to contain a predominant B-cell epitope. However, the recognition of this exposed epitope by an anti-HBc antibody appeared to be affected by the I97E mutation or by histidine tagging at the C terminus of mutant HBcAg, which is presumably in the capsid interior. Surprisingly, the nuclear HBcAg of mutants I97E and I97W, produced from either a replicon or an expression vector, was found to be colocalized with nucleolin and B23 at a frequency of nearly 100% by confocal immunofluorescence microscopy. In contrast, this colocalization occurred with wild-type HBcAg only to a limited extent. We also noted that nucleolin-colocalizing cells were often binucleated or apoptotic, suggesting that the presence of HBcAg in the nucleolus may perturb cytokinesis. The mechanism of this phenomenon and its potential involvement in liver pathogenesis are discussed. To our knowledge, this is the first report of nucleolar HBcAg in culture.

Wild type and YMDD variant of hepatitis B virus: No difference in viral kinetics on lamivudine/tenofovir therapy in HIV–HBV co-infected patients

2006 ◽  
Vol 36 (1) ◽  
pp. 60-63 ◽  
Author(s):  
T.E.M.S. de Vries-Sluijs ◽  
A.A. van der Eijk ◽  
B.E. Hansen ◽  
A.D.M.E. Osterhaus ◽  
R.A. de Man ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Wild Type ◽  
Viral Kinetics ◽  
B Virus
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