Interaction of Flaviviruses with Reproduction Inhibitors Binding in β-OG Pocket: Insights from Molecular Dynamics Simulations

Flaviviral diseases, including dengue fever, West Nile fever, yellow fever, tick-borne encephalitis, Omsk haeorr agic fever, and Powassan encephalitis, threaten human health all over he world. Lack of effective antiviral targeting replication cycle of flaviviruses makes the search of such compounds a challenging task. Recently we have identified a reproduction inhibitor effective against tickborne encephalitis virus and Powassan virus (POWV) (ACS Med. Chem. Lett., 2013, 4, 869-874). To enable using this inhibitor as a template for 3D pharrnacophore search a o- logically ac e conformation of h s molecule should have been established. Here we performed molecular dynamics ulations of the complexes between the different enaniomers of he inhibitor and POWV envelope (E) proteins, putative targets of he inhibitor, in the different protona ion states corresponding to the different stages of membrane fusion process. Several stable conformations of the inhibitor were identified, opening routes for u he design of ore advanced molecules.