Extended Data Fig. 5: UH15-38 prevents lethality in severe influenza.
From: Necroptosis blockade prevents lung injury in severe influenza
a, Weight loss curves of mice infected with PR8 (6000 EID50; ~LD100) followed by i.p. administration of vehicle (n = 20) or the following doses of UH15-38: 50 mg/kg (n = 20), 30 mg/kg (n = 21), 15 mg/kg (n = 15), 7.5 mg/kg (n = 15). Vehicle or UH15-38 was administered once-daily per the dosing schedule shown above the graph. b, c, Survival graphs (b) and weight loss curves (c) of mice (n = 10) infected with PR8 (6000 EID50) and treated with vehicle (n = 12) or with UH15-38 (30 mg/kg, i.p.) for a shortened-, or delayed-dosing regimens, as indicated above panel b. d, e, Survival (d) and weight loss (e) curves of mice (n = 7) infected with PR8 (4500 EID50) and treated i.p. with vehicle or GSK′872 (30 mg/kg) as indicated above the graph. f, Weight loss analysis of mice infected with IAV H1N1 strain A/California/04/09 (600 EID50; ~LD60) and treated once-daily with either vehicle (n = 10) or UH15-38 (30 mg/kg, i.p., n = 13) per the dosing schedule shown above the graph. g, Weight loss curves of mice infected with PR8 (4500 EID50; ~LD60) and treated i.p. with UH15-38 (30 mg/kg, i.p.), per dosing regimens shown above the graph (drug treatment beginning at day 3 after infection, n = 9; all other groups, n = 10/group). h, Wild type mice or Mlkl –/– mice (n = 10) were infected with PR8 (2500 EID50). Wild type mice were treated with either vehicle (n = 10) or 30 mg/kg UH15-38 (n = 12) once daily for four days starting 24 h after infection. i, Wild type mice or Mlkl –/– mice (n = 15) were infected with PR8 (4500 EID50). Wild type mice were treated with either vehicle (n = 14) or 30 mg/kg UH15-38 (n = 13) once daily for four days starting 24 h after infection. Mice were observed until 21 days and survival curves were plotted. Wild-type (Mlkl+/+) mice in panels h and i were generated by intercrossing Mlkl+/– mice. Groups were compared using the Log-rank (Mantel-Cox) test.
