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Supplemental methods Phylogenetic relationship of the Zika virus with other Flaviviruses 131 whole genome sequences were obtained from Genbank containing representative member of Zika Virus, Japanese Encephalitis Virus, Yellow fever Virus, West Nile virus and Dengue Virus. All sequences were aligned using the MAFFT server using default parameters. A maximum likelihood tree was reconstructed using the General Time Reversible model and the tree with the highest log likelihood (-165576.1058) is shown. Initial tree(s) for the heuristic search were obtained by applying the Neighbor-Joining method to a matrix of pairwise distances estimated using the Maximum Composite Likelihood (MCL) approach. A discrete Gamma distribution was used to model evolutionary rate differences among sites (5 categories (+G, parameter = 1.1760)). Results were validated using 100 bootstrap replicates and the tree was plotted using FigTree. Molecular phylogenetic analysis of Zika viral evolution 29 unique whole genome sequences of Zika virus were obtained from GenBank and aligned using the MAFFT server using default parameters. Maximum Likelihood phylogenetic trees were reconstructed based on the General Time Reversible model. All positions with less than 95% site coverage were eliminated. That is, fewer than 5% alignment gaps, missing data, and ambiguous bases were allowed at any position. There were a total of 10239 positions in the final dataset. The initial tree(s) for the heuristic search were obtained by applying the Neighbor-Joining method to a matrix of pairwise distances estimated using the Maximum Composite Likelihood (MCL) approach. A discrete Gamma distribution was used to model evolutionary rate differences among sites (5 categories (+G, parameter = 0.2856)). 1000 bootstrap replicates were utilized to validate and generate a condensed tree (50 % cutoff value). Evolutionary analyses were conducted in MEGA6. 1 Supplemental Figures Figure S1 Fig. S1. Phylogeny of the flavi-viruses A cladogram representing the phylogenetic relationship of the Zika virus with other closely related flaviviruses like Dengue, Japanese Encephalitis, Yellow fever and West Nile Virus obtained using the Maximum Likelihood method based on the General Time Reversible model. The tree is obtained from 100 bootstrap replicates using Mega6 and drawn as a cladogram using Figtree. 2 The individual virus types group into distinct clades and are colored for easy visualization and the relevant sub-strain types are labelled accordingly.Among the flavivirus family, the four groups have been suggested to be phylogeneticallyrelated to Zika viruses, including Dengue virus (in green), Yellow fever virus (in blue), Japanese encephalitis virus (in black), and West nile virus (in purple). The Zika virus group is in red, of which two subclades (Asian-American lineage and African lineage) are proposed and highlighted in yellow background. Figure S2 Fig. S2. Structures of envelope glycoproteins The structures of West Nile Virus (a), Japanese Encephalitis Virus (b) and Zika virus (c) envelope glycoproteins are colored cyan, magenta, and green. Domains I, II and III are defined by orange lines and superposed (d), suggesting these structures are highly similar to each other. Figure S3 3 Fig. S3. The electrostatic potential surfaces of the E protein of three Flaviviruses The electrostatic potential surfaces of West Nile Virus (a), Japanese Encephalitis Virus (b) and Zika virus (c) envelope glycoproteins. Domain III of Zika virus envelope glycoprotein is more positively charged than those of West Nile Virus and Japanese Encephalitis Virus envelope glycoproteins. 4