In Vitro Anti-hepatitis B Virus Activity of 2′,3′-Dideoxyguanosine

Abstract

2 0 ,3 0-dideoxyguanosine (DoG) has been demonstrated to inhibit duck hepatitis B virus (DHBV) replication in vivo in a duck model of HBV infection. In the current study, the in vitro antiviral effects of DoG on human and animal hepadnaviruses were investigated. Our results showed that DoG effectively inhibited HBV, DHBV, and woodchuck hepatitis virus (WHV) replication in hepatocyte-derived cells in a dose-dependent manner, with 50% effective concentrations (EC 50) of 0.3 ± 0.05, 6.82 ± 0.25, and 23.0 ± 1.5 lmol/L, respectively. Similar to other hepadnaviral DNA polymerase inhibitors, DoG did not alter the levels of intracellular viral RNA but induced the accumulation of a less-than-full-length viral RNA species, which was recently demonstrated to be generated by RNase H cleavage of pgRNA. Furthermore, using a transient transfection assay, DoG showed similar antiviral activity against HBV wild-type, 3TC-resistant rtA181V, and adefovirresistant rtN236T mutants. Our results suggest that DoG has potential as a nucleoside analogue drug with anti-HBV activity.

The Efficacy of an Empowerment Program for End-Stage Renal Disease Patients Treated with Hemodialysis

“…Then they were respectively loaded onD101, DM301, X-5 and AB-8 resins. Next, they were eluted with distilled water 25%, 50% and 75% ethanol and the eluent were collected for anti-HSV-1 experiments [16].…”

Synthesis of 1,2,3‐Triazole‐Linked Hexopyranosylpyrimidine Nucleosides and Their Application as Hepatitis B Viral DNA, HBsAg and HBeAg Suppressants

“…[24,25] However, prolonged administration of the nucleoside drugs may result in the evolution of drug-resistant mutants of hepatitis B virus. [24][25][26][27] Various research groups have reported the frequency of HBV drug resistance-associated mutations (RAM) from different populations across the world based on public sequence databases. [28] Thus, there is a continuing need to develop wide range of nucleoside analogues with increased therapeutic indices and drug resistant barriers.…”

“…Similarly, 2′,3′‐dideoxyguanosine ( 8 ) exhibited potent antiviral effects on human and animal hepadnaviruses and found to be highly effective against 3‐TC and adefovir resistant mutants (Figure 1). [24] …”

“…Chronic hepatitis B virus (HBV) remains a serious health hazard affecting almost 250 million people worldwide [24] . Food and Drug Administration (FDA) have approved five nucleos(t)ide analogues for anti‐HBV therapy, i. e ., lamivudine (3TC), telbivudine (LdT), adefovir (ADV), tenofovir (TDF) and entecavir (ETV) [24] . The nucleos(t)ide analogues inhibit DNA replication by chain termination of viral DNA or RNA elongation [24,25] .…”

“…Similarly, 2',3'-dideoxyguanosine (8) exhibited potent antiviral effects on human and animal hepadnaviruses and found to be highly effective against 3-TC and adefovir resistant mutants (Figure 1). [24] Herein, we report the synthesis of novel 1,2,3-triazole linked hexopyranosyl mono/double-headed pyrimidine nucleosides 15 a-b and 20 a-b from D-glucose via click chemistry. The synthesized nucleosides were examined for their anti hepatitis B virus activity on HepG2.2.15 cell line.…”