*2.9. Structural Alignment*

The following model and structures were aligned to HCV RdRP complexed with RNA, Mn2<sup>+</sup>, and sofosbuvir-DP (PDB 4WTD [34]) using Pymol [35]: 1) a model of ZIKV RdRP in complex with RNA, Mn2<sup>+</sup> ions, and an incoming ADP modified to an ATP (gc-o3 [36]) generated from ZIKV RdRP stucture PDB 5TFR [37] (160 atoms aligned, RMS = 1.650); 2) a crystal structure of apo ZIKV RdRP (PDB 5WZ3 [38]) (154 atoms aligned, RMS = 2.860); and 3) a crystal structure of apo HCV RdRP (PDB 3MWV [39]) (530 atoms aligned, RMS = 0.874).
