Fig. 4. Tetrandrine inhibits EBOV infection both in vitro and in vivo.

(A) Macrophages were treated with tetrandrine (8 μM) and then infected with EBOV-GFP. After 48 h, the frequency of GFP positive cells was calculated and normalized to untreated controls. The data are mean ± SD (n = 3) and representative of two independent experiments. (B) Female Balb/c mice injected intraperitoneally with mouse-adapted EBOV were treated with 30 mg/kg of tetrandrine or control saline on days 0, 1, 3, 5 and 7 (n = 8 for each group). Survival curves are shown. * P = 0.0008 by log-rank (Mantel-Cox) test. (C and D) Clinical scores of EBOV-infected mice. Disease signs included weight loss, rough hair coat, squinty eyes, hunched back, moderate unresponsiveness, labored breathing and persistent prostration. Based on these criteria, a clinical score for each day was calculated and plotted (individually indicated by symbols) for the untreated animals (C) or tetrandrine-treated animals (D). (E) Virus titer in sera of infected mice was measured by plaque assays. * P = 0.006 by unpaired Student's t test. (F) Delayed treatment of EBOV-challenged mice. Female Balb/c mice injected intraperitoneally with mouse-adapted EBOV were treated with 30 mg/kg or 90 mg/kg of tetrandrine or control saline on days 1, 3, 5 and 7 (n = 7 for each group). Survival curves are shown * P = 0.04 by log-rank (Mantel-Cox) test comparing to untreated animals.