Illustrating and homology modeling the proteins of the Zika virus

The Zika virus (ZIKV) is a flavivirus of the family Flaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guillain-Barré syndrome and microcephaly. Although ZIKV has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. No antivirals have been tested against it either in vitro or in vivo. ZIKV therefore epitomizes a neglected disease. Several suggested steps have been proposed which could be taken to initiate ZIKV antiviral drug discovery using both high throughput screens as well as structure-based design based on homology models for the key proteins. We now describe preliminary homology models created for NS5, FtsJ, NS4B, NS4A, HELICc, DEXDc, peptidase S7, NS2B, NS2A, NS1, E stem, glycoprotein M, propeptide, capsid and glycoprotein E using SWISS-MODEL. Eleven out of 15 models pass our model quality criteria for their further use. While a ZIKV glycoprotein E homology model was initially described in the immature conformation as a trimer, we now describe the mature dimer conformer which allowed the construction of an illustration of the complete virion. By comparing illustrations of ZIKV based on this new homology model and the dengue virus crystal structure we propose potential differences that could be exploited for antiviral and vaccine design. The prediction of sites for glycosylation on this protein may also be useful in this regard. While we await a cryo-EM structure of ZIKV and eventual crystal structures of the individual proteins, these homology models provide the community with a starting point for structure-based design of drugs and vaccines as well as a for computational virtual screening

Switching Off Electron Transfer Reactions in Confined Media: Reduction of [Co(dipic)₂]⁻ and [Co(edta)]⁻ by Hexacyanoferrate(II)

The kinetics of reduction of two cobalt­(III) complexes with similar redox potentials by hexacyanoferrate­(II) were investigated in water and in reverse micelle (RM) microemulsions. The RMs were composed of water, surfactant [(sodium­(bis­(2-ethylhexylsulfosuccinate)), NaAOT], and isooctane. Compared to the reaction in water, the reduction rates of (ethylenediaminetetraacetato)­cobaltate­(III) by hexacyanoferrate­(II) were dramatically suppressed in RM microemulsions whereas a slight rate increase was observed for reduction of bis-(2,6-dipicolinato)­cobaltate­(III). For example, the ferrocyanide reduction of [Co­(dipic)₂]⁻ increased from 55 M^–1 s^–1in aqueous media to 85 M^–1 s^–1 in a <i>w</i>_o = 20 RM. The one-dimensional (1-D) and two-dimensional (2-D) ¹H NMR and FT-IR studies are consistent with the reduction rate constants of these two complexes being affected by their location within the RM. Since reduction of [Co­(edta)]⁻ is switched off, in contrast to [Co­(dipic)₂]⁻, these observations are attributed to the penetration of the [Co­(edta)]⁻ into the interfacial region of the RM whereas [Co­(dipic)₂]⁻ is in a region highly accessible to the water pool and thus hexacyanoferrate­(II). These results demonstrated that compartmentalization completely turns off a redox reaction in a dynamic microemulsion system by either reactant separation or alteration of the redox potentials of the reactants