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

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

Since for the first time, a flavivirus helicase was co-crystallized with bound ATP at substrate binding site; therefore this structure seems more significant for inhibitor screening purpose (as shown in figure 1A ). Similarly, another crystal structure has ssRNA bound at helicase active site which appears suitable for employing virtual screening protocol (as shown in figure 2A ). We have used extra precision (XP) mode in glide suite of Schrödinger to dock EGCG firstly at ATPase site and after that at helicase site (as shown in figure 1 and figure 2 respectively). After docking, the extent of EGCG binding at ATPase site was represented in terms of docking score as shown in table 1. A significant docking score (-7.8 Kcal mol -1 ) was observed which is contributed by various hydrogen bonding interactions with key residues of ATPase site such as ARG (202), THR (201), GLY (197), ASN (463), and ASN (417) (as shown in figure 1B, 1C and table1). Another important interaction was observed with ARG (462) which shows salt bridge and Pi-cation bonding with EGCG ( figure 1B and 1C ). More importantly, these interactions were reported at the critical P-loop (residues193-203) and motif VI (residues Q455, R459, and R462) of NTPase binding pocket. Mechanistic studies have already shown that P-loop residues play the most significant contribution in NTP binding and further hydrolysis (21, 31) .