Discovery of Potential Antiviral Compounds against Hendra Virus by Targeting Its Receptor-Binding Protein (G) Using Computational Approaches

Hendra virus (HeV) belongs to the paramyxoviridae family of viruses which is associated with the respiratory distress, neurological illness, and potential fatality of the affected individuals. So far, no competitive approved therapeutic substance is available for HeV. For that reason, the current research work was conducted to propose some novel compounds, by adopting a Computer Aided Drug Discovery approach, which could be used to combat HeV. The G attachment Glycoprotein (Ggp) of HeV was selected to achieve the primary objective of this study, as this protein makes the entry of HeV possible in the host cells. Briefly, a library of 6000 antiviral compounds was screened for potential drug-like properties, followed by the molecular docking of short-listed compounds with the Protein Data Bank (PDB) structure of Ggp. Docked complexes of top two hits, having maximum binding affinities with the active sites of Ggp, were further considered for molecular dynamic simulations of 200 ns to elucidate the results of molecular docking analysis. MD simulations and Molecular Mechanics Energies combined with the Generalized Born and Surface Area (MMGBSA) or Poisson–Boltzmann and Surface Area (MMPBSA) revealed that both docked complexes are stable in nature. Furthermore, the same methodology was used between lead compounds and HeV Ggp in complex with its functional receptor in human, Ephrin-B2. Surprisingly, no major differences were found in the results, which demonstrates that our identified compounds can also perform their action even when the Ggp is attached to the Ephrin-B2 ligand. Therefore, in light of all of these results, we strongly suggest that compounds (S)-5-(benzylcarbamoyl)-1-(2-(4-methyl-2-phenylpiperazin-1-yl)-2-oxoethyl)-6-oxo-3,6-dihydropyridin-1-ium-3-ide and 5-(cyclohexylcarbamoyl)-1-(2-((2-(3-fluorophenyl)-2-methylpropyl)amino)-2-oxoethyl)-6-oxo-3,6-dihydropyridin-1-ium-3-ide could be considered as potential therapeutic agents against HeV; however, further in vitro and in vivo experiments are required to validate this study.     

Semiconductor nanoparticles for photoinitiation of free radical polymerization in aqueous and organic media

Photoinduced free radical polymerization of vinyl monomers by using semiconductor inorganic nanoparticles (NPs) is investigated. Zinc oxide and iron‐doped zinc oxide were used as photosensitive compounds to initiate the polymerization of acrylamide as a water‐soluble monomer in aqueous environment and methyl methacrylate as an oil‐soluble monomer in organic media under UV‐light irradiation. The method uses photochemically generated electrons and holes from the NPs to form initiating hydroxyl radicals in aqueous media, while tertiary amines and iodonium salt served as coinitiator in organic media. The initiation mechanism in organic media involves hydrogen abstraction or reduction processes via charge carriers, respectively. The kinetic of the polymerization in both environments was studied by means of a photo‐differential scanning calorimetry. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1500–1507     

Tetrapyrrole bizirconium complexes as active catalysts for ethylene polymerization

Ethylene polymerization was carried out by using a group of new dizirconium(IV) tetrapyrrole complexes as catalysts and MAO as co-catalyst under 1 atmosphere pressure of ethylene gas at 25 and 40°C. The highest value of catalyst activity was obtained at 40°C by using bizirconium complexes including one calix[4]pyrrole between two zirconium centers and two terminal chlorines, while zirconium(IV) complexes with coordinated THF, almost have not catalytic activity. The maximum catalytic activity mounted to 830 kg/mol·bar·h by Zr₂(Cy₄ Pyr ₄)Cl₄. The results show that the structure of the coordination sphere of zirconium(IV) has great influence on the rate of polymerization, molar masses of forming polymer, and its molecular mass distribution. Correspondence: Sajjad Mohebbi, Chemistry Department, University of Kurdistan, P.O. Box 66176-416, Sanandaj, Iran.     

Structural,Optical and Electrical Properties of Cu0.6CoxZn0.4−xFe2O4 (x = 0.0, 0.1, 0.2, 0.3, 0.4) Soft Ferrites

A series of cobalt-inserted copper zinc ferrites, Cu_0.6Co_xZn_0.4−xFe₂O₄ (x = 0.0, 0.1, 0.2, 0.3, 0.4) having cubic spinel structure were prepared by the coprecipitation method. Various characterization techniques, including XRD, FTIR, UV-vis and I–V were used to investigate structural optical and electrical properties, respectively. The lattice constant was observed to be decreased as smaller ionic radii Co²⁺ (0.74 Å) replaced the higher ionic radii Zn²⁺ (0.82 Å). The presence of tetrahedral and octahedral bands was confirmed by FTIR spectra. Optical bandgap energy was determined in the range of 4.44–2.05 eV for x = 0.0 to 0.4 nanoferrites, respectively. DC electrical resistivity was measured and showed an increasing trend (5.42 × 10⁸ to 6.48 × 10⁸ Ω·cm) with the addition of cobalt contents as cobalt is more conductive than zinc. The range of DC electrical resistivity (10⁸ ohm-cm) makes these nanomaterials potential candidates for telecommunication devices.     

Facile Synthesis of 5-Aryl-N-(pyrazin-2-yl)thiophene-2-carboxamides via Suzuki Cross-Coupling Reactions,Their Electronic and Nonlinear Optical Properties through DFT Calculations

Synthesis of 5-aryl-N-(pyrazin-2-yl)thiophene-2-carboxamides (4a–4n) by a Suzuki cross-coupling reaction of 5-bromo-N-(pyrazin-2-yl)thiophene-2-carboxamide (3) with various aryl/heteroaryl boronic acids/pinacol esters was observed in this article. The intermediate compound 3 was prepared by condensation of pyrazin-2-amine (1) with 5-bromothiophene-2-carboxylic acid (2) mediated by TiCl₄. The target pyrazine analogs (4a–4n) were confirmed by NMR and mass spectrometry. In DFT calculation of target molecules, several reactivity parameters like FMOs (E_HOMO, E_LUMO), HOMO–LUMO energy gap, electron affinity (A), ionization energy (I), electrophilicity index (ω), chemical softness (σ) and chemical hardness (η) were considered and discussed. Effect of various substituents was observed on values of the HOMO–LUMO energy gap and hyperpolarizability. The p-electronic delocalization extended over pyrazine, benzene and thiophene was examined in studying the NLO behavior. The chemical shifts of ¹H NMR of all the synthesized compounds 4a–4n were calculated and compared with the experimental values.     

Synthesis of fully substituted pyrano[2,3-c]pyrazole derivatives via a multicomponent reaction of isocyanides

The three-component reaction of the zwitterions generated from dialkyl acetylenedicarboxylate and isocyanides with 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one is described. The reaction afforded the corresponding special type of fully substituted pyrano[2,3-c]pyrazole derivatives in good yields without using any catalyst and activation.     

Spin density polarization effects in the presence of Coriolis force on ion acoustic waves in quantum plasma

Ion acoustic solitary waves in a quantum plasma, which is slowly rotating around an axis at an angle θ with the direction of magnetic field, are investigated. Quantum hydrodynamic model is under consideration with the effects of rotations which are included via Coriolis force. Fermions are degenerate and have different spin density states, that is, up and down characterized via parameter α. Linear analysis is performed by applying Fourier transformation to derive dispersion relation. For nonlinear analysis, we apply reductive perturbation method to derive Korteweg de Vries equation (KdV). The effects of variations of Coriolis force, spin polarization, and quantum parameter on characteristics of solitary structure are discussed. These results are applicable to astrophysical and laboratory plasmas.