Combinatorial Computational Approaches to Identify Tetracycline Derivatives as Flavivirus Inhibitors
The residues affecting the pH threshold of fusion are indicated. (A) The crystal conformation is shown in the CPK model (i.e., oxygen in red, nitrogen in blue, and carbon in gray), and the docked conformation of the BOG is shown in yellow. The formation of the hydrogen bonds is shown by a green dashed line. The RMSD of the conformations is 1.20 Å, and both pre-fusion and post-fusion conformations form hydrogen bonds with Glu49 and Gln271. (B) The docked conformations of the 10 selected compounds are shown. The four tetracycline derivatives are colored (doxycycline in green, rolitetracycline in blue, tetracycline in orange, and oxytetracycline in red). The inhibitory compounds (doxycycline and rolitetracycline) are docked in the vicinity of residues Thr48, Glu49, Ala50, Lys51, and Gln52.