Indeed, using a chemical chaperone, 4-PBA, that inhibits the PERK and the ATF6 pathways and potentiates the IRE1α pathway, we achieved a significant 3.74-log (5,623-fold) reduction in virus titer, suggesting that potent inhibition of ZIKV infection may require synergistic manipulation of the three UPR arms. This evidence concerns the gene ERN1 and Zika virus infectious disease.