Figure 1.
Chemical structures of FNC and 3TC.
Table 1.
Anti-HIV-1 activities of FNC, 3TC and AZT in cell culturesa.
Table 2.
Anti-HIV-1 activities of FNC, 3TC and AZT against RT-resistant strains in C8166 cellsa.
Figure 2.
Quantification of HIV-1 DNA species. ssDNA (A) and late-RT (B). All experiments were conducted in the presence or absence of 2nM FNC and 2 µM 3TC. Each group was tested in triplicates and data are presented as mean ± standard deviations (SD).
Table 3.
Effect of in vitro antiviral activity of FNC in combination with approved antiretroviral drugs in C8166.
Table 4.
Genotypic patterns of HIV-1IIIB selected by FNC and 3TC.
Figure 3.
The binding of FNCTP and 3TCTP to the polymerase active site of RT.
The binding mode of FNCTP and 3TCTP to RT of wild type and mutant forms (A). Top-panel and bottom-panel show the overview and close-up view of the binding mode of compounds FNC and 3TC, with DC as a control. Secondary structural elements were colored from blue (N-terminus) to red (C-terminus). The compounds FNCTP, 3TCTP and DCTP are colored with red, blue and green, respectively. The motif YMDD residues are shown as sticks. The spheres models of compounds FNCTP and 3TCTP interacting with residue184 of RT in wild-type M184 (B) and mutant forms V184 (C), I184 (D) are shown in the figure. The β-branched side chains of the residues V/I184 have steric hindrance with azido group of FNCTP and S atom at oxathiolane ring of 3TCTP.
Figure 4.
The interactions of FNC, 3TC and DC with residue 214 of RT.
The interactions of FNC,3TC and DC with residues 214 and 160 of RT are shown. FNC, 3TC and DC are colored with red, blue and green, respectively. The residues 214,160 are shown as sticks. The distances between three compounds and the residues 214 and 160 are measured and shown by dashed yellow line.