hdpp4 mice prophylactically  (Gilead Sciences)

Journal: Nature Communications

Article Title: Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV

doi: 10.1038/s41467-019-13940-6

Figure Lengend Snippet: a Percent starting weight of 9–12-week-old male and female Ces1c −/− hDPP4 mice prophylactically administered subcutaneous vehicle or remdesivir (RDV, 25 mg/kg) BID the day prior to infection with either 5E + 04 (vehicle n = 14, RDV n = 14) or 5E + 05 (vehicle n = 14, RDV n = 15) plaque-forming units (pfu) MERS M35C4. Asterisks indicate statistically significant differences ( P < 0.05) as determined by two-way ANOVA and Tukey’s multiple comparison test. b Percent survival of each cohort and survival analysis by Mantel–Cox test ( P < 0.05, N per group noted in a ). c Lung hemorrhage scored on a scale of 0–4, where 0 is a normal pink healthy lung and 4 is a completely dark red lung. On 4 dpi, N = 4/group, and on 6 dpi the remaining animals are plotted. Asterisks indicate statistically significant differences ( P < 0.05) as determined by two-way ANOVA and Tukey’s multiple comparison test. d MERS-CoV lung titer on 4 ( N = 4) and 6 dpi (all remaining animals). Asterisks indicate statistically significant differences ( P < 0.05) as determined by two-way ANOVA and Sidek’s multiple comparison test. For a , c , d , the boxes encompass the 25th to 75th percentile, the line is at the median, while the whiskers represent the range. e Hematoxylin (nuclei, blue) and immunostaining for MERS-CoV antigen (brown) in lung tissue sections from 4 dpi. All photos were taken with the same magnification. The black bar indicates 100 µM scale. Images from representative mice for each group are shown.

Article Snippet: Fig. 2 Prophylactic RDV reduces MERS-CoV replication and disease. a Percent starting weight of 9–12-week-old male and female Ces1c −/− hDPP4 mice prophylactically administered subcutaneous vehicle or remdesivir (RDV, 25 mg/kg) BID the day prior to infection with either 5E + 04 (vehicle n = 14, RDV n = 14) or 5E + 05 (vehicle n = 14, RDV n = 15) plaque-forming units (pfu) MERS M35C4.

Techniques: Infection, Immunostaining

Journal: Nature Communications

Article Title: Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV

doi: 10.1038/s41467-019-13940-6

Figure Lengend Snippet: 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.

Article Snippet: Fig. 2 Prophylactic RDV reduces MERS-CoV replication and disease. a Percent starting weight of 9–12-week-old male and female Ces1c −/− hDPP4 mice prophylactically administered subcutaneous vehicle or remdesivir (RDV, 25 mg/kg) BID the day prior to infection with either 5E + 04 (vehicle n = 14, RDV n = 14) or 5E + 05 (vehicle n = 14, RDV n = 15) plaque-forming units (pfu) MERS M35C4.

Techniques: Infection, MANN-WHITNEY, Whisker Assay

Journal: Nature Communications

Article Title: Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV

doi: 10.1038/s41467-019-13940-6

Figure Lengend Snippet: Percent starting weight of 10–12-week-old female Ces1c −/− hDPP4 mice infected with 5E + 04 pfu MERS M35C4 and treated with a subcutaneous vehicle for RDV ( N = 13) or remdesivir (RDV, 25 mg/kg, N = 14) BID beginning 1 dpi or b vehicle for LPV/RTV-IFNb ( N = 15), LPV/RTV-IFNb low ( N = 16) or LPV/RTV-IFNb high ( N = 16) beginning 1 dpi. Oral vehicle or lopinavir/ritonavir (160/40 mg/kg) was administered orally once daily. IFNb low (1x human equivalent dose of 1.6 MIU/kg) and high (25x human equivalent dose of 40 MIU/kg) or PBS vehicle were administered via subcutaneous injection every other day. Asterisks indicate statistical differences by two-way ANOVA with Tukey’s multiple comparison test. c Lung hemorrhage 6 dpi for all animals in a , b scored on a scale of 0–4, where 0 is a normal pink healthy lung and 4 is a diffusely discolored dark red lung. d MERS-CoV lung titer 6 dpi in mice as described in a , b . Asterisks indicate statistical significance ( N group described in a and b , P < 0.05) by one-way ANOVA with Kruskal–Wallis test for ( c , d ). Data for a – d are compiled from two independent experiments. 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. e Representative photomicrographs of MERS-CoV antigen (brown) and hematoxylin stained nuclei (blue) in mouse lung tissue sections from 6 dpi. The black bar is 100 µM.

Article Snippet: Fig. 2 Prophylactic RDV reduces MERS-CoV replication and disease. a Percent starting weight of 9–12-week-old male and female Ces1c −/− hDPP4 mice prophylactically administered subcutaneous vehicle or remdesivir (RDV, 25 mg/kg) BID the day prior to infection with either 5E + 04 (vehicle n = 14, RDV n = 14) or 5E + 05 (vehicle n = 14, RDV n = 15) plaque-forming units (pfu) MERS M35C4.

Techniques: Infection, Injection, Whisker Assay, Staining