scholarly journals Inhibitory effects of selected antiviral compounds on human hepatitis B virus DNA synthesis.

1991 ◽  
Vol 35 (2) ◽  
pp. 394-397 ◽  
Author(s):  
T Yokota ◽  
S Mochizuki ◽  
K Konno ◽  
S Mori ◽  
S Shigeta ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Dna Synthesis ◽  
Inhibitory Effects ◽  
Hepatitis B Virus Dna ◽  
Antiviral Compounds ◽  
Human Hepatitis ◽  
B Virus

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 Base Pairing between cis-Acting Sequences Contributes to Template Switching during Plus-Strand DNA Synthesis in Human Hepatitis B Virus

2007 ◽  
Vol 81 (12) ◽  
pp. 6207-6215 ◽  
Author(s):  
Eric B. Lewellyn ◽  
Daniel D. Loeb
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Dna Synthesis ◽  
Template Switching ◽  
Base Pairing ◽  
Cis Acting ◽  
Duck Hepatitis ◽  
Human Hepatitis ◽  
B Virus ◽  
Template Switches

ABSTRACT Hepadnaviruses utilize two template switches (primer translocation and circularization) during synthesis of plus-strand DNA to generate a relaxed-circular (RC) DNA genome. In duck hepatitis B virus (DHBV) three cis-acting sequences, 3E, M, and 5E, contribute to both template switches through base pairing, 3E with the 3′ portion of M and 5E with the 5′ portion of M. Human hepatitis B virus (HBV) also contains multiple cis-acting sequences that contribute to the accumulation of RC DNA, but the mechanisms through which these sequences contribute were previously unknown. Three of the HBV cis-acting sequences (h3E, hM, and h5E) occupy positions equivalent to those of the DHBV 3E, M, and 5E. We present evidence that h3E and hM contribute to the synthesis of RC DNA through base pairing during both primer translocation and circularization. Mutations that disrupt predicted base pairing inhibit both template switches while mutations that restore the predicted base pairing restore function. Therefore, the h3E-hM base pairing appears to be a conserved requirement for template switching during plus-strand DNA synthesis of HBV and DHBV. Also, we show that base pairing is not sufficient to explain the mechanism of h3E and hM, as mutating sequences adjacent to the base pairing regions inhibited both template switches. Finally, we did not identify predicted base pairing between h5E and the hM region, indicating a possible difference between HBV and DHBV. The significance of these similarities and differences between HBV and DHBV will be discussed.

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