Broad-Spectrum Antiviral Therapeutics
(A) Multiple 100 nM DRACOs were effective against 130 pfu/well rhinovirus (4 dpi). Even better performance of these alternate DRACOs might be achieved with further optimization. (B) PKR-Apaf DRACOs reduced the viral titer in supernatant from NHLF cells challenged with 300 pfu/well rhinovirus 1B to undetectable levels. PKR and Apaf-1 domains not covalently linked increased viral titers somewhat, possibly by interfering with the antiviral activity of endogenous wild-type PKR and Apaf-1. Cells were treated with 100 nM DRACO or controls. Supernatants were collected 4 dpi and their viral titers determined by serial dilution onto fresh 96-well NHLF plates. (C) The EC50 for PTD-PKR-Apaf DRACO was 2–3 nM against 130 pfu/well rhinovirus 1B in NHLF cells (measured 3 dpi), and 50 pfu/well murine encephalomyelitis (3 dpi) and 50 pfu/well murine adenovirus (11 dpi) in L929 cells.