Fig. 5. Prophylactic treatment with GS-5734 reduces SARS-CoV disease.

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Fig. 5. Prophylactic treatment with GS-5734 reduces SARS-CoV disease. Prophylactic treatment with GS-5734 reduces SARS-CoV disease. (A) Percent starting weight of Ces1c−/− mice infected with 104 PFU SARS-CoV MA15 treated beginning at −1 dpi with either vehicle (n = 42) or GS-5734 [25 mg/kg BID (n = 25) or 50 mg/kg QD (n = 28)]. (B) SARS-CoV lung titer of mice in (A) at 2 dpi (vehicle, n = 11; 50 mg/kg, n = 11; 25 mg/kg, n = 5) (left) or 5 dpi (vehicle, n = 13; 50 mg/kg, n = 13; 25 mg/kg, n = 4) (right). n.s., not significant. (C) Quantitation of SARS-CoV antigen in lung sections of mice in (A) at 2 dpi (left) (vehicle, n = 15; 50 mg/kg, n = 12; 25 mg/kg, n = 7) (left) or 5 dpi (vehicle, n = 10; 50 mg/kg, n = 12; 25 mg/kg, n = 4) (right). (D) Photomicrographs of SARS-CoV antigen staining (brown) and nuclei (blue) in lung sections from 2 and 5 dpi. (E) Photomicrographs of hematoxylin and eosin–stained mouse lung sections from 2 dpi highlighting the conducting airway lumen (aw). (F) WBP was used to measure the pulmonary function of mice in (A). Penh is a surrogate measure of bronchoconstriction. Expiration time (te) is the time taken to release one breath. End of expiratory pause (EEP) is the time between breaths. Symbols and error bars for (A), (B), (D), and (I) represent the mean and SD. The boxes encompass the 25th to 75th percentile, whereas the whiskers represent the range in (C), (E), and (F). Asterisk indicates statistical significance (P < 0.05) by two-way analysis of variance (ANOVA) with Tukey’s multiple comparison test for (D), (F), and (I) and with Kruskal-Wallis test for (E). Timothy P. Sheahan et al., Sci Transl Med 2017;9:eaal3653 Published by AAAS