Fig. 4: Prophylactic LPV/RTV + IFNb does not improve disease outcomes.

a Percent starting weight (Left) of 12–14-week-old female Ces1c^−/− hDPP4 mice infected with 5E + 04 pfu MERS M35C4 and treated BID with either vehicle (n = 9) or remdesivir (RDV, 25 mg/kg, n = 9) subcutaneously beginning −1 dpi. Asterisks indicate statistically significant differences (P < 0.05) as determined by two-way ANOVA and Tukey’s multiple comparison test. (Middle) MERS-CoV lung titer on 2 (N = 3) and 6 dpi (all remaining animals). Asterisks indicate statistically significant differences (P < 0.05) as determined by Mann–Whitney test. (Right) WBP was used to assess pulmonary function in mice. PenH is a surrogate measure of airway resistance or bronchoconstriction. Asterisks indicate statistical differences by two-way ANOVA with Sidek’s multiple comparison test. b Percent starting weight (left), virus lung titer (middle), and pulmonary function metric PenH (right) of cohorts of mice similar in age and sex and infected similarly with MERS-CoV as in b but treated with vehicle (n = 9), LPV/RTV + IFNb low (1× human equivalent) (n = 9), LPV/RTV + IFNb high (25× human equivalent) (n = 9), or IFNb high only (n = 9). Oral vehicle or lopinavir/ritonavir (160/40 mg/kg) were administered orally once daily beginning the −1 dpi. IFNb treatment was initiated 2 h prior to infection and every other day thereafter. To control for dosing effects, vehicle-treated mice received both LPV/RTV vehicle and subcutaneous PBS to mirror IFNb injections. Likewise, IFNb only group received oral vehicle to mirror that seen in orally dosed groups. Similar statistical tests performed on a were performed on b. For the box and whisker plots, the boxes encompass the 25th to 75th percentile, the line is at the median, while the whiskers represent the range.