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. 2017 Aug 1;8:167. doi: 10.1038/s41467-017-00170-x

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Administration of RSV fusion inhibitors reduces infection in animal models. a Dose-dependent inhibition of infectious RSV titer in lavaged-lung tissue of male, 6–8-week-old infected cotton rats treated with a single dose of JNJ-53718678 1 h before infection. Shown on the graphs are the individual data points measured (green circles); bars represent mean values (n = 15). b Relative dose-dependent inhibition of RSV mRNA expression in lung tissue of male, 6–8-week-old infected cotton rats treated with a single dose of JNJ-53718678 1 h before infection. mRNA expression in cotton rats treated with different single doses of JNJ-53718678 was calculated relative to the vehicle-treated animals (set as 100 %). Green bars represent average values + s.e.m. (n = 15). c Inhibition of the infectious RSV titer in BALF (purple bars) and lavaged-lung tissue (green bars) of 5–15-week-old infected cotton rats of both sexes treated with a single dose (Tx1; n = 4) or multiple once-daily doses (Tx2; n = 10) of 40 mg kg⁻¹ JNJ-53718678 starting 24 h after infection. Titers of compound-treated animals were compared to the titers in animals treated with vehicle only (vehicle; n = 9) on Day 4 after infection. As a positive control for viral growth in the lungs of animals in the absence of treatment with JNJ-53718678, RSV titers were determined in BALF and lavaged-lung tissue at 5 h after intranasal inoculation (VL 5 h; n = 10) and compared to the titers on Day 4. Bars represent average values + s.e.m. d, e Inhibition of the infectious RSV titer d and RSV viral RNA levels e in BALF (purple bars) and lavaged-lung tissue (green bars) of 1–3-day-old infected neonatal lambs of both sexes treated once daily with 1 (n = 4), 5 (n = 3), or 25 (n = 3) mg kg⁻¹ of JNJ-53718678 or with vehicle only (0; n = 3) as indicated on the x-axis. Bars represent average values + s.e.m. f Treatment-dependent inhibition of infectious RSV titer in BALF of 1–3-day-old infected neonatal lambs of both sexes treated once daily with 25 mg kg⁻¹ JNJ-49214698 starting 24 h before (Px; n = 4)) or 72 h after infection (Tx; n = 5) and compared to the titer in vehicle only-treated (n = 4) or non-infected (n = 5) animals. Red dotted line indicated the lower limit of quantification (LLOQ) or detection (LLOD) of the respective assays. Statistical analysis in all panels was performed by one-way ANOVA followed by Dunnett’s post hoc. *p-value < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001