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

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

In recent years, repeated outbreaks of ZIKV has necessitated the urgent need for developing specific drugs. Also, the major complications of ZIKV infections are related to pregnant women, therefor it is important to find molecules which are safe and have minimal or no side-effects. Considering the safety point, natural products have always been a great source of drugs or drug like molecules and also these molecules have evolutionary preoptimized biological targets (8) . To find specific biological targets, in silico structure-based drug discovery approaches have revolutionized and fasten the current drug developing strategies. In fact, the molecules which can target specifically viral proteins could act as safe therapeutics against ZIKV (34) . EGCG, a green tea polyphenol has shown significant antiviral activity against several viruses including HIV, HSV, CHIKV and some flaviviruses like HCV, and DENV (10) . Recently, in ZIKV, EGCG inhibitory potential was determined in a cell line based study where probable mechanism was related to interaction of the compound with envelope protein (16) . Previously, we have also supported the EGCG envelope protein interaction with computational study (17) . However, reports suggested that EGCG may target other viral proteins which are important in genome replication and maturation (10) . Due to lack of adequate experimental support regrading EGCG envelope protein interactions and considering the possibility of finding more specific target for EGCG, we have chosen NS3 helicase protein of ZIKV for determining potential inhibitory effects of EGCG. NS3 helicase of ZIKV is an attractive drug target due to its essential role in opening RNA secondary structures during replication (21) . Also, reports suggest that EGCG has shown anti-ATPase activity against bacterial DNA gyrases(33).