Zika virus is a mosquito-borne flavivirus responsible for congenital Zika syndrome, microcephaly, and fetal demise. There are no vaccines or antivirals available to treat this virus. NS2A protein encoded by Zika virus is essential for genome packaging and virus assembly. By Affinity Purification and Mass Spectrometry, we identified a set of Dead Box Helicase proteins interacting with NS2A. Using shRNA knockdown experiments we reveal novel roles of dead box helicases in flavivirus assembly process.