PAR1 agonist or antagonist dose-dependent effect on hMPV infection during a 3-day treatment in mice.

<p>Groups of 12 mice were infected intranasally with hMPV (4-6 x10⁵ TCID₅₀) or mock infected and simultaneously treated for 3 days with a single daily dose of 50 or 500 µM of PAR1 agonist (TFLLR-NH₂), PAR1 antagonist (SCH79797) or their respective vehicles. A) and B) Weight loss and mortality were monitored daily for 14 days for mice treated with the PAR1 agonist and antagonist, respectively. The horizontal bar underneath the graphic indicates the timing and duration of treatment. Arrows and numbers indicate the mice that reached the endpoint and were sacrificed (full line: mice treated with 50 µM of PAR1 agonist, dotted line: mice treated with 500 µM of PAR1 agonist). Significant differences in weight loss were observed between mice treated with 50 µM (†) or 500 µM (*) of compound compared to untreated mice based on a two-way ANOVA (* p<0.05, ** p<0.01, *** p<0.001, † p<0.05, † † p<0.01). C) Viral titers were determined by TCID₅₀ in lung homogenates at day 5 pi. Significant differences were observed between treated or untreated mice as determined by one-way ANOVA. (* p<0.05, ** p<0.01) The bar indicates the lower limit of detection.