Mechanistic insights into Zika virus NS3 helicase inhibition by Epigallocatechin-3-gallate: Supplementary Files

Deepak Kumar; Nitin Sharma; Murali Aarthy; Sanjeev Singh; Rajanish Giri

Among those, (−)-Epigallocatechin-3-gallate (EGCG), a green tea polyphenol has shown great virucidal potential against flaviviruses including ZIKV. However, the mechanistic understanding of EGCG targeting viral proteins is not yet entirely deciphered except little is known about its interaction with viral envelope protein and viral protease. Since literature has shown significant inhibitory interactions of EGCG against various kinases and bacterial DNA gyrases; we designed our study to find inhibitory actions of EGCG against ZIKV NS3 helicase. NS3 helicase is playing a significant role in viral replication by unwinding RNA after hydrolyzing NTP. We employed molecular docking and simulation approach and found significant interactions at ATPase site and also at RNA binding site. Further, the enzymatic assay has shown significant inhibition of NTPase activity with an IC50 value of 295.7 nM and Ki of 0.387 ± 0.034 µM. Our study suggests the possibility that EGCG could be considered as prime backbone molecule for further broadspectrum and multitargeted inhibitor development against ZIKV and other flaviviruses.