Fig. 2. Prophylactic efficacy of GS-621763.
a Single-dose PK study in ferrets showing plasma concentrations of GS-441524, GS-621763, and remdesivir (RDV) as specified after dosing with GS-621763 (30 mg/kg; p.o.; red “+” symbols), remdesivir (10 mg/kg; i.v.; blue “×” symbols), and GS-441524 (20 mg/kg; i.v.; green triangles). Symbols represent individual biological repeats (n = 3), lines depict sample means. b, Schematic of the prophylactic efficacy study design. Ferrets were infected intranasally with 1 × 105 pfu WA1/2020 (virus symbol). Groups (n = 4) were gavaged b.i.d. (first aid symbol) with vehicle or GS-621763 (20 mg/kg) starting at the time of infection. Nasal lavages (pipet symbol) were harvested twice daily. All animals were terminated 4 days after infection. c Virus titers from nasal lavages; LoD, limit of detection. d Temperature measurements collected once daily. e Body weight measured once daily. f Infectious titers of SARS-CoV-2 in nasal turbinates harvested four days after infection. g SARS-CoV-2 RNA copies present in nasal lavages. h, SARS-CoV-2 RNA copies detected in nasal turbinates. i–j SARS-CoV-2 infectious particles (i) and SARS-CoV-2 RNA copies (j) in lungs four days after infection. Symbols for vehicle-treated and GS-621763 treated ferrets are shown as black and red circles, respectively (c–j). The number of independent biological repeats (individual animals) is shown in each subpanel, symbols represent independent biological repeats, lines (c–e, g) and bar graphs (f, h–j) connect or show samples mean, respectively, and P values are stated. 2-way ANOVA with Sidak’s post hoc multiple comparison tests (c–e, g) or two-tailed t test (f, h).