Fig. 11

Modeling BIC and CAB into the PFV Intasome. The four panels show models of DTG, CAB, or BIC bound in the active site of HIV-1 IN. The upper left panel a shows a model of DTG (cyan) bound to HIV-1 IN. The upper right panel b shows a model of CAB (green) bound to the active site of the HIV-1 IN using DTG (cyan) as the template. The lower left panel c shows a model of BIC (magenta) bound to the active site of HIV-1 IN using DTG (cyan) as the template. The lower right panel d shows an overlay of the binding of DTG (cyan), BIC (magenta), and CAB (green) to HIV-1 IN, specifically showing how the “left-side” of these three INSTIs, the part of pharmacophores distal from the end of the viral DNA, interact with HIV-1 IN. All four panels show the Mg²⁺ cofactors rendered in space-filling format (slate gray) interacting with the chelating motifs of each of the INSTIs. HIV-1 IN is depicted in multi-colored ribbons with active site residues D64, D116, and E152 labeled in red and rendered in dark gray ball and stick format