Inhibition of hepatitis B virus by a novel L-nucleoside, β-L-D4A and related analogues

Figure 1 Structures of β-L-D4A and analogues.

Figure 2 Inhibition of isomers of D4A and D2A on HBV DNA replication in supernatant. Lane 1 as negative control; lanes 2, 3, 4 as D-D2A at 2 μM, 4 μM and 8 μM, respectively; lanes 5, 6, 7 as L-D2A at 2 μM, 4 μM and 8 μM, respectively; lanes 8, 9, 10 as D-D4A at 2 μM, 4 μM and 8 μM, respectively; lanes 11, 12, 13 as L-D4A at 2 μM, 4 μM and 8 μM, respectively. RC: relaxed circular HBV DNA; SS: single-stranded HBV DNA.

Figure 3 Inhibition on replication of extracellular HBV DNA by β-L-D4A. lanes 1, 2 as negative control; lanes 3, 4 as lamivudine at 1 μM; lanes 5, 6 as β-L-D4A at 10 μM; lanes 7, 8 as β-L-D4A at 2 μM; lanes 9, 10 as β-L-D4A at 0.4 μM; lanes 11, 12 as β-L-D4A at 0.08 μM; lanes 13, 14 as blank control (HepaG₂). RC: relaxed circular HBV DNA; SS: single-stranded HBV DNA.

Figure 4 Inhibition on replication of extracellular HBV DNA by β-L-D4A.

Figure 5 Inhibition on replication of intracellular HBV DNA by β-L-D4A. lane 1 as negative control; lane 2 as lamivudine at 1 μM; lane 3 as β-L-D4A at 10 μM; lane 4 as β-L-D4A at 2 μM; lane 5 as β-L-D4A at 0.4 μM; lane 6 as β-L-D4A at 0.08; lane 7 as blank control (HepaG2). RC: relaxed circular HBV DNA; SS: single-stranded HBV DNA.

Figure 6 Toxicity of mitochondrial DNA. lane 1 as blank control; lane 2 as β-L-D4A at 0.4 μM; lane 3 as β-L-D4A at 10 μM; lane 4 as ddC at 0.4 μM.

Figure 7 Effect of β-L-D4A on cell growth curve.