Therapeutic targeting of organelles for inhibition of Zika virus replication in neurons.

Zika virus (ZIKV) is an arbovirus belonging to the family Flaviviridae. Since 2015, ZIKV infection has emerged as a leading cause of virus-induced placental insufficiency, microcephaly and other neuronal complications. Currently, no therapeutics have been approved to treat ZIKV infection. In this study, we examined how targeted inhibition of cellular organelles or trafficking processes affected ZIKV infection and replication in neural progenitor cells. We found that blocking endocytosis, Golgi function or structural filaments like actin or microtubules had moderate effects on virus replication. However, inducing endoplasmic reticulum (ER) stress by treatment with Thapsigargin substantially inhibited virus production, suggesting the ER might be a candidate cellular target. Further analysis showed that sarcoplasmic/endoplasmic reticulum Ca2+-ATPases (SERCA) was important for ZIKV inhibition. Collectively, these studies indicate that targeting the SERCA-dependent ER stress pathway may be useful to develop antivirals to inhibit ZIKV replication.