FIG 3.

Influence of therapy delay when human pharmacokinetic profiles were simulated for EIDD-1931. (A) A549 cells that stably expressed ACE2 were mixed with SARS-CoV-2 (MOI = 10 to 5) and inoculated into the hollow fiber infection model (HFIM). EIDD-1931 was administered into hollow fiber (HF) cartridges to mimic human pharmacokinetic profiles associated with 800 mg once daily (Q24h) or 400 mg twice daily (Q12h). Therapy was initiated 24 h (tx at 24 h) or 48 h (tx at 48 h) after infection for both dosage regimens. One HF cartridge did not receive the drug, serving as a no-treatment control, and one cartridge received a high dose (3.5 μg/mL) of EIDD-1931 as a continuous infusion served as a positive control. Cartridges were sampled daily, and the infectious viral burden was measured by plaque assay on Vero E6 cells. Data points correspond to the mean ± one standard deviation of two biological replicates and the dashed line signifies the plaque assay limit of detection. Two independent studies were conducted. (B) Medium samples from the central reservoir of each HFIM system were taken multiple times throughout the first 48 h to ensure the desired PK profiles were achieved. Concentrations of EIDD-1931 were quantified via liquid chromatography-tandem mass spectrometry.