Schematic overview of the Zika virus (ZIKV) genome. The ZIKV genome is a single-stranded positive-sense RNA (+ssRNA) of approximately 11 Kb and codes a polyprotein which is cleaved in the endoplasmic reticulum (ER) lumen by the host and/or viral proteases to release three structural proteins (C, PrM and E; red boxes) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5; yellow boxes). The 5′ untranslated region (UTR) is susceptible for specific double methylation (represented in grey box at left) by the viral C-terminal methyltransferase domain of NS5 to behave like messenger RNA (mRNA) and hijacks host factors for translation and for masking the viral RNA to prevent cellular recognition and degradation. UTR loops at 3′ end are subgenomic flavivirus RNAs (sfRNAs) (shown in the grey box on the right), that play a role in the immune response evasion (see Section 2.4 in the main text).