The Viral Polymerase Inhibitor 7-Deaza-2’-C-Methyladenosine Is a Potent Inhibitor of In Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model
Fig 5
In vivo efficacy of 7DMA against ZIKV. AG129 mice (male, 8–14 weeks of age; n = 9) were treated with 50 mg/kg/day 7DMA sodium carboxymethylcellulose (CMC-Na)] via oral gavage or with vehicle [0.5% or 0.2% CMC-Na; n = 9] for 10 days.
Mice were infected intraperitoneally with 200 μL of a 1×104 PFU/mL stock of ZIKV 1 hour after the first treatment on day 0. (A) Percentage survival between ZIKV-infected mice treated with vehicle (● and ■) or 7DMA (○ and □) was compared using the Log-rank (Mantel-Cox) test. Data represent results from 2 independently performed studies. (B) Viral RNA load in serum on day 1, 2, 3, 5, 6, 7 and 8 pi of ZIKV-infected mice treated with vehicle (white boxes) or 7DMA (grey boxes), as determined by RT-qPCR. Statistical analysis was performed using the unpaired, two-tailed t-test. Data are representative of 2 independent experiments. (C) Viral RNA load in testicles of vehicle-treated, ZIKV-infected AG129 mice at day 5 pi, as determined by RT-qPCR. (D) Expression at different time points pi of IFN-γ in sera of ZIKV-infected mice treated with vehicle (white boxes) or 7DMA (grey boxes), as determined using the ProcartaPlex Mouse IFN- γ, IL-18, IL-6, IP-10, TNF-α Simplex kit (e-Bioscience). Data represent results from 2 independent experiments.