EGCG inhibits ZIKV independent of GRP78. A549 cells were treated with either (a) honokiol (HNK) or (b) epigallocatechin-gallate (EGCG) at indicated concentrations for 26 h. Cell viability was measured relative to a DMSO control as indicated by the line graph. Separately, A549 cells were treated with the same drug concentrations for 2 h prior to infection with ZIKV-Nanoluc (MOI 0.1) for 24 h. Nanoluc readings are relative to a DMSO control indicated by the bar graph. (c) EGCG (10 µM) was added to A549 cells and maintained throughout a 24 h ZIKV-Nanoluc infection or added 1 h or 4 h post-removal of virus inoculum. Nanoluc values were measured relative to a DMSO vehicle control. (d) ZIKV-Nanoluc was incubated with either DMSO or EGCG (10 µM) independently of cells for 2 h at 37 °C. Simultaneously, A549 cells were treated with DMSO or EGCG for 2 h before the drug containing media was replaced with drug treated or DMSO treated control virus for 1 h. Following this, virus inoculum was removed and replaced with DMEM containing either DMSO or EGCG as before for a further 23 h. Error bars represent the standard error of the mean of triplicate repeats. An unpaired Student’s t-test with Welch’s correction was used to determine statistical significance where n.s = not significant, * p-value < 0.05, ** p-value < 0.01 and *** p-value < 0.001. (a–d) n = 3.