Binding pattern and susceptibility of epigallocatechin gallate against envelope protein homodimer of Zika virus: A molecular dynamics study

Zika virus (ZIKV) has caused an infant neurologic disorder, microcephaly, leading to a global health problem. Until now, no antiviral drug against ZIKV is commercially available. The recent studies reported that epigallocatechin gallate (EGCG) was found as a potential agent inhibiting the ZIKV entry process in Vero E6 cell. A pH-induced conformational change of the viral envelope (E) protein is a key step in such process. Herein, we focused on how EGCG could inhibit the dimeric E protein at the three possible binding sites at acidic pH condition by all-atom molecular dynamics (MD) simulations for 500 ns. The three EGCG binding sites on dimeric E protein are (i) the hinge region between domains I and III; (ii) the conserved region among flaviviruses; and (iii) the dimer interface. As a result, the binding pattern of EGCG in each pocket was presented in the mode of action of inhibition. The ligand-protein binding interactions, protein motions and binding free energies indicated that EGCG favorably interacted with the conserved region greater than the hinge region and the dimer interface, respectively. The obtained results via 4 different end-point free energy calculation methods suggested how this compound binds and prevents the rearrangement in the E protein at low pH. (C) 2018 Published by Elsevier B.V.