Fig. 4. GS-621763 blocks replication and transmission of SARS-CoV-2 VOC γ a, Schematic of the efficacy and contact transmission study design.

All ferrets were infected intranasally with 1 × 10⁵ pfu BZ/2021 (virus symbol). Symbols as described for Fig. 2a. Groups of ferrets (n = 4) were gavaged b.i.d. with vehicle (black circles in b–g) or GS-621763 (10 mg/kg; red squares in b–g) starting at 12 h after infection. Nasal lavages were harvested twice daily. On the second day after infection, vehicle and GS-621763 ferrets were cohoused with untreated contact ferrets (black open circles and red open squares for vehicle and GS-621763 contact ferrets, respectively). Source ferrets were terminated 4 days after infection and all contact animals were terminated on study day 8. b Virus titers from nasal lavages. c, SARS-CoV-2 RNA copies present in nasal lavages. d Infectious titers of SARS-CoV-2 in nasal turbinates harvested four days after infection. e SARS-CoV-2 RNA copies detected in nasal turbinates. f Infectious titers of SARS-CoV-2 in lung tissue. g SARS-CoV-2 RNA copies present in lung tissue. In (b–g), the number of independent biological repeats (individual animals) is shown in each subpanel. Symbols represent independent biological repeats, lines (b, c) and bar graphs (d–g) connect or show sample means, respectively, and P values are stated. 1-way (d, e) or 2-way (b, c) ANOVA with Tukey’s (d, e) or Sidak’s (b, c) post hoc multiple comparison tests. h, Metagenome sequence analysis of inoculum WA1/2020 (blue bar; black diamonds; n = 1) and BZ/2021 (red bar; black circles; n = 1) viruses, BZ/2021 RNA extracted from ferret nasal turbinates four days after infection (red bars; black squares and downward pointing triangles for vehicle (n = 4) and GS-621763 treated (n = 4) ferrets, respectively), WA1/202 RNA extracted from ferret nasal turbinates four days after infection (blue bars; black hexagons and “×” symbols for vehicle (n = 4) and GS-621763 treated (n = 4) ferrets, respectively) and BZ/2021 populations extracted from nasal lavages of contacts of vehicle-treated source animals (red bars; black upward pointing triangles; n = 3). Relative allele frequencies of signature residues are shown. Symbols represent independent biological repeats (virus population of individual animals), columns show group means. LoD limit of detection.