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

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

One of such natural products is a polyphenol called EGCG which constitutes major fraction (59 % of all polyphenols) of green tea polyphenols and has shown multiple health benefits such as antitumor, antimicrobial, antioxidative and antiviral, etc (10) . The antiviral role of EGCG has been well demonstrated against several viruses such as hepatitis C virus (HCV), human immunodeficiency virus (HIV), influenza virus (FLU), DENV and chikungunya virus, etc (11) (12) (13) (14) (15) . In a recent study, EGCG has shown a strong virucidal effect against ZIKV with a probable mechanism related to inhibiting entry into host cell demonstrated by computational finding (16, 17) . However, reports suggest that apart from viral entry inhibition EGCG can also block essential steps in the replication cycle of some viruses (10) . Due to the lack of complete understanding of EGCG inhibition mechanism on ZIKV, we designed our study to find a specific viral protein which could be targeted by EGCG. We have chosen NS3 helicase protein of ZIKV, a crucial enzyme in viral replication which unwinds genomic RNA after deriving energy from intrinsic nucleoside triphosphatase (NTPase) activity (18, 19) . In addition to RNA unwinding activity, flavivirus helicases have also been reported to participate in other vital functions such as ribosome biogenesis, pre-mRNA splicing, RNA export and degradation, RNA maturation as well as translation etc (20) . Hence, essential functions of these helicases are making them attractive drug targets.