Fig. 3: Prophylactic oral treatment with GS-441524 of AG129 mice intranasally inoculated with HPIV3 reduces viral loads and lung pathology.
a Setup of the study. AG129 mice were orally treated twice daily with either vehicle or 50 mg/kg GS-441524 from day −1 p.i. to day 2 p.i., and intranasally inoculated with 1.5 × 106 TCID50 of HPIV-3 at day 0 p.i. Lung samples were collected at day 3 p.i. to measure viral loads. b Infectious virus titers are expressed as log10 TCID50 per milligram of lung sample. LLOD presents the lower limit of detection. c HPIV-3 RNA levels are expressed as log10 TCID50 equivalent per milligram of lung sample. LLOQ presents the lower limit of quantification. b, c Data are from two independent experiments, each with 6 mice per group. Data were analyzed by the two-tailed Mann–Whitney U test. ****p < 0.0001. d Setup of the study. AG129 mice were orally treated twice daily with vehicle or 50 mg/kg GS-441524 from day −1 p.i. to day 5 p.i., and intranasally inoculated with 1.5 × 106 TCID50 of HPIV-3 at day 0 p.i. Lungs were collected at day 6 p.i. for lung histopathology assessment. e Weight change at day 6 p.i. is presented as a percentage of the body weight at day −1 p.i., when treatment was started. f Representative H&E-stained images reveal normal lung parenchyma in uninfected mice, centrilobular accentuation of inflammation with bronchopneumonia (green arrows), perivascular inflammation (red arrows), and peribronchial inflammation (blue arrows) in the vehicle-treated mice, and very focal and limited perivascular inflammation (red arrows) in the GS-441524-treated mice. The scale bar is 50 µm. The samples of uninfected mice and infected mice were from the same experiment, but the staining procedure was performed at different moments. g Cumulative severity scores of lungs of all infected mice. e, g Data are from one experiment with 8 mice in the vehicle-treated group and 7 mice in the GS-441524-treated group. Data were analyzed with the two-tailed Mann–Whitney U test. ns nonsignificant, ***p = 0.0002. Individual data and median values (indicated by bars) are presented in all graphs. Source data are provided as a Source Data file. a, d were designed with BioRender.
