Extended Data Fig. 5: JNJ-9676 and reference compounds as pre- or post-exposure treatment in Syrian golden hamsters infected with SARS-CoV-2 B1.
From: A small-molecule SARS-CoV-2 inhibitor targeting the membrane protein
a, Single-dose pharmacokinetic profiles of JNJ-9676 in Syrian golden hamster. Mean ± standard deviations (n = 3 animals/group). b, Pre-exposure treatment with 8.33, 25 or 75 mpk JNJ-9676 or 200 mpk molnupiravir (n = 5 animals/group). Percentage bodyweight change on day 4. Individual data points (n = 5 animals/group) represent mean ± standard deviation. Mean differences between groups are calculated using one-way ANOVA with Šídák’s multiplicity correction. c-f, Post-exposure treatment with 75mpk JNJ-9676 or 250 mpk nirmatrelvir (treatment one hour before infection or 10 h after infection) (n = 5 animals in the vehicle group, n = 8 animals in other groups). c,d, Individual data points (n = 5 animals/group) represent mean ± standard deviation. Mean differences between groups are estimated as in b. c, Viral load in the lung. Values below the limit of detection (LOD) were imputed to 3.89 log10 copies/mL (LOD value). p = 0.0001 for JNJ-9676-1 h.p.i. versus vehicle, p = 0.0039 for JNJ-9676+10 h.p.i. versus vehicle, p = 0.0310 for NTV+10 h.p.i. versus vehicle. d, Infectious virus in the lung. Values below the LOD were imputed to 3 log10 plaque-forming units/g (LOD value). p < 0.0001 for JNJ-9676-1 h.p.i. versus vehicle, p < 0.0001 for JNJ-9676+10 h.p.i. versus vehicle, p = 0.0243 for NTV+10 h.p.i. versus vehicle, p = 0.0109 for JNJ-9676-1 h.p.i. versus NTV+10 h.p.i. and p = 0.0035 for JNJ-9676+10 h.p.i. versus NTV+10 h.p.i. e,f, Individual data points per group (median and 95% confidence intervals). Differences between groups are calculated using the non-parametric Kruskal-Wallis test with the original false discovery rate method of Benjamini and Hochberg multiplicity correction. e, Histopathology score in the lung. p = 0.0009 for JNJ-9676-1 h.p.i. versus vehicle, p = 0.0009 for JNJ-9676+10 h.p.i. versus vehicle. f, Immunohistology in the lung. p = 0.0017 for JNJ-9676-1 h.p.i. versus vehicle, p = 0.0017 for JNJ-9676+10 h.p.i. versus vehicle. g,h, Post-exposure treatment with 75 mpk JNJ-9676 or 250 mpk nirmatrelvir (treatment 10-, 24- or 48-hours post-infection)(n = 5 animals/group). Mean differences between groups are estimated as in b. g, Mean body weight ± standard deviation over time. h, Mean percentage bodyweight change ± standard deviation on day 4. Mean differences between groups are estimated as in b. p = 0.0066 for JNJ-9676+10 h.p.i. 75 mkp BID. h.p.i., hours post-infection; BID, twice daily; mpk, milligrams/kilogram bodyweight; LOD, limit of detection. The doses reflect the amount of compound given each administration.
