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Additional file 1: Table S1. Data collection and refinement statistics. Table S2. Structure-based sequence alignment of ILHV and DENV-4. Table S3. The binding site for ILHV helicase before and after mutation. Table S4. The target protein docking results for ATP and Mn2+. Table S5. Summary of the ATPase activities of the ILHV helicase mutants. Table S6. The ATPase activity comparison of different flaviviruses. Table S7. The docking results for ST-610 and Suramin with ILHV helicase. Figure S1. Purification of ILHV helicase using gel filtration chromatography. Figure S2. Superimpositions of the crystal structure of ILHV helicase with different forms of ZIKV helicase. Figure S3. Structural alignment of the helicase domains of different flaviviruses. Figure S4. The NTP hydrolysis site and comparison with ZIKV of the ILHV helicase. Figure S5. The binding mode of ATP, Mn2+ with the wild-type ILHV helicase and three mutants. Figure S6. The overlap structures of three mutants before and after mutation. Figure S7. The RMSD plot and RMSF plot during molecular dynamics simulations of protein with ATP. Figure S8. The binding modes of ILHV helicase with ST-610 and Suramin.