title: Interaction of Flaviviruses with Reproduction Inhibitors Binding in β-OG Pocket: Insights from Molecular Dynamics Simulations.
abstract: Flaviviral diseases, including dengue fever, West Nile fever, yellow fever, tick-borne encephalitis, Omsk haemorrhagic fever, and Powassan encephalitis, threaten human health all over the world. Lack of effective antivirals targeting replication cycle of flaviviruses makes the search of such compounds a challenging task. Recently we have identified a reproduction inhibitor effective against tick-borne encephalitis virus and Powassan virus (POWV) (ACS Med. Chem. Lett., 2013, 4, 869-874). To enable using this inhibitor as a template for 3D pharmacophore search, a biologically active conformation of this molecule should have been established. Here we performed molecular dynamics simulations of the complexes between the different enantiomers of the inhibitor and POWV envelope (E) proteins, putative targets of the inhibitor, in the different protonation states corresponding to the different stages of membrane fusion process. Several stable conformations of the inhibitor were identified, opening routes for further design of more advanced molecules.
authors.affiliation: Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia phone: +7-495-939-39-69, fax: +7-495-939-02-90.|Chumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow 142782, Russia.|iScalare Laboratory, Moscow Institute of Physics and Technology, Dolgoprudny 141700, Russia.
authors.forename: Evgenia V
authors.initials: EV
authors.lastname: Dueva
authors.affiliation: Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia phone: +7-495-939-39-69, fax: +7-495-939-02-90.|Chumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow 142782, Russia.|iScalare Laboratory, Moscow Institute of Physics and Technology, Dolgoprudny 141700, Russia.
authors.forename: Dmitry I
authors.initials: DI
authors.lastname: Osolodkin
authors.affiliation: Chumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow 142782, Russia.
authors.forename: Liubov I
authors.initials: LI
authors.lastname: Kozlovskaya
authors.affiliation: Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia phone: +7-495-939-39-69, fax: +7-495-939-02-90. vap@qsar.chem.msu.ru.|iScalare Laboratory, Moscow Institute of Physics and Technology, Dolgoprudny 141700, Russia. vap@qsar.chem.msu.ru.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Palyulin
authors.affiliation: iScalare Laboratory, Moscow Institute of Physics and Technology, Dolgoprudny 141700, Russia.
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Pentkovski
authors.affiliation: Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia phone: +7-495-939-39-69, fax: +7-495-939-02-90.
authors.forename: Nikolay S
authors.initials: NS
authors.lastname: Zefirov
keywords: Antivirals; Envelope proteins; Flavivirus; Molecular dynamics; Powassan virus