IRE1α inhibitors prevent ZIKV-induced cell death. (A+B) Cells were treated with small molecule inhibitors or DMSO solvent control prior to infection with ZIKV. Viability was measured four days post-infection by quantifying ATP in metabolically active cells. (A) The IRE1α kinase inhibitor KIRA6 and nuclease inhibitor STF-083010 prevent loss of viability during ZIKV infection. (B) The IRE1α nuclease inhibitor 4μ8C, but not AMC, a structurally similar negative control compound, prevents ZIKV-induced loss of viability. (C) Wildtype (WT) and IRE1α knockodown (KD) cells were infected with ZIKV and viability was measured three days post-infection. Data are means ± SD of three replicates and are representative of at least two independent experiments. * p < 0.01, ** p < 0.001, by unpaired t test.