HCMV and HSV-1 DNA polymerase structures and chemical formulas of pyrophosphate analogues, 5-substituted 2′-deoxyuridine analogues, and nucleoside analogues. HCMV and HSV-1 DNA polymerase structures and chemical formulas of pyrophosphate analogues, 5-substituted 2′-deoxyuridine analogues, and nucleoside analogues. (A) Tertiary structures of HCMV DNA polymerase in complex with dsDNA and foscarnet (PDB accession number 3KD5). HCMV DNA polymerase is shown in pink. The dsDNA is placed in the center, where foscarnet inhibits DNA synthesis at the active site of HCMV DNA polymerase. Structural movies that demonstrate drug binding are available online (see http://www.virusface.com/). PyMOL V1.7 visualization software (http://www.pymol.org/) was used. (B) Tertiary structures of HSV-1 DNA polymerase complexed with dsDNA and ATP (PDB accession numbers 2GV9 and 4M3R). HSV-1 DNA polymerase is shown in pink. ATP near the catalytic site is displayed in the drug-binding pocket. The triphosphate form of approved antiviral inhibitors (e.g., vidarabine triphosphate) can compete with dATP to inhibit the replication activity of HSV DNA polymerase. (C) Chemical formula of foscarnet in the group of pyrophosphate analogues. (D to F) Chemical formulas of idoxuridine, trifluridine, and brivudine in the group of 5-substituted 2′-deoxyuridine analogues. (G to J) Chemical formulas of telbivudine, entecavir, vidarabine, and FV100 in the group of nucleoside analogues. Note that FV100 is an experimental inhibitor in phase 3 clinical trials. Erik De Clercq, and Guangdi Li Clin. Microbiol. Rev. 2016; doi:10.1128/CMR.00102-15