The inhibitory performance of flavonoid cyanidin-3-sambubiocide against H274Y mutation in H1N1 influenza virus

<p>Oseltamivir (Tamiflu) is the most accepted antiviral drug that targets the neuraminidase (NA) protein to inhibit the viral release from the host cell. Few H1N1 influenza strains with the H274Y mutation creates drug resistance to oseltamivir. In this study, we report that flavonoid cyanidin-3-sambubiocide (C3S) compound acts as a potential inhibitor against H274Y mutation. The drug resistance mechanism and inhibitory activity of C3S and oseltamivir against wild-type (WT) and H274Y mutant-type (MT) have been studied and compared based on the results of molecular docking, molecular dynamics, and quantum chemical methods. Oseltamivir has been found less binding affinity with MT. C3S has more binding affinity with WT and MT proteins. From the dynamical study, the 150th loop of the MT protein has found more deformation than WT. A single H274Y mutation induces the conformational changes in the 150th loop which leads to produce more resistance to oseltamivir. The 150th cavity is more attractive target for C3S to stop the conformational changes in the MT, than 430th cavity of NA protein. The C3S is stabilized with MT by more number of hydrogen bonds than oseltamivir. The electrostatic interaction energy shows a stronger C3S binding with MT and this compound may be more effective against oseltamivir-resistant virus strains.</p

Computational studies of pandemic 1918 and 2009 H1N1 hemagglutinins bound to avian and human receptor analogs

<div><p>The purpose of this work was to study the binding properties of two pandemic influenza A virus 1918 H1N1 (SC1918) and 2009 H1N1 (CA09) hemagglutinin (HA) with avian and human receptors. The quantum chemical calculations have been performed to analyze the interactions of 130 loop, 190 helix, 220 loop region, and conserved residues 95,145,153–155, of pandemic viruses’ HA with sialo-trisaccharide receptor of avian and human using density functional theory. The HA’s residues Tyr 95, Ala 138, Gln 191, Arg 220, and Asp 225 from the above regions have stronger interaction with avian receptor. The residues Thr 136, Trp 153, His 183, and Asp 190 of HA are important and play a significant role to bind with human receptor. The residues Tyr 95, Ala 138, Lys 145, Trp 153, Gln 192, and Gln 226 of HA of CA09 virus have found more interaction energies with human than avian receptors. Due to mutations in the active residues of HA of CA09 virus comparing with SC1918, the binding capabilities of HA with human have been increased. The molecular dynamics simulation was made to understand the different dynamical properties of HA and molecular interactions between HA of these two viruses with sialo-trisaccharide receptors of avian and human receptors. The interaction energy of HA of CA09 virus with human receptor decreases due to the human receptor far away from conserved residue region of HA protein. This reveals that the conserved residues particularly Lys 145 play major contribution to interaction with human receptor in HA of CA09 virus.</p></div

Dy³⁺ Occupancy in Zirconia Lattice Affects Tetragonal to Cubic Phase Transitions in Zirconia Toughened Alumina Systems

Current research on zirconia toughened alumina (ZTA) systems employed in total hip joint replacement applications is focused on the usage of alternative stabilizers to improve their properties. Herein, a wide range of dysprosium (Dy³⁺) additions to ZTA systems have been formed through an in situ method. Dy³⁺ induced significant structural changes in ZrO₂ rather than the α-Al₂O₃ component of the composite. Dy³⁺ tends to occupy along the <i>a</i> = <i>b</i>-axis of the ZrO₂ lattice to stabilize tetragonal zirconia (<i>t</i>-ZrO₂), whereas its enhanced accumulation directed the formation of cubic zirconia (<i>c</i>-ZrO₂). As a consequence of phase transition, a different behavior in the emission characteristics was also noticed. However, <i>t</i>- → <i>c</i>-ZrO₂ phase transition was not found to affect the paramagnetic behavior of Dy³⁺ added ZTA systems. The structural stability of the Dy³⁺ added ZTA systems was preserved until 1500 °C, and moreover it was also determined that optimum Dy³⁺ content is essential for enhanced mechanical stability of the composite

Doxorubicin-Conjugated Bimetallic Silver–Gadolinium Nanoalloy for Multimodal MRI-CT-Optical Imaging and pH-Responsive Drug Release

Monodispersed chitosan-capped bimetallic nanoparticles (BNPs) of AgGd have been synthesized for “cancer theranosis” through environmentally benign microwave-assisted polyol synthesis. In the present article, we report the one-pot synthesis of AgGd BNPs with varied Ag:Gd molar ratios via coreduction of Ag⁺ and Gd³⁺ ions. Studies reveal a well-dispersed AgGd BNPs of average size 12 nm and also the presence of face-centered cubic (FCC) Ag and cubic Gd components within the individual crystal. Chitosan (CS) a biopolymer, as a capping agent facilitates the bioconjugation of doxorubicin (Dox), a potential anticancer drug on the surface of BNPs. The Dox was covalently conjugated onto the BNPs through pH-sensitive hydrazone linkage with CS. In vitro study reveals negligible drug release at physiological pH while release rate accelerates in acidic medium. The mutual properties of the host metals in AgGd BNPs at the nanoscale offer concurrent magnetic resonance imaging (MRI) and computed tomography (CT) contrast performances. Moreover, the paramagnetic behavior inherited by Gd in BNPs demonstrates both <i>T</i>₁ and <i>T</i>₂ contrast ability. BNPs ensures biocompatibility and also express sturdy therapeutic effects in HeLa cells when conjugated with Dox

Crystallization and Polymorphic Phase Transitions in Zirconia-Toughened Alumina Systems Induced by Dy³⁺/Gd³⁺ Cosubstitutions

The substitution of rare earth elements in zirconia-toughened alumina (ZTA) to expand the resultant material properties forms a crux of the investigation in recent years. In this work, the simultaneous substitutions of Gd³⁺ and Dy³⁺ in ZTA and the subsequent variation in the structural, mechanical, and magnetic imaging characteristics are demonstrated. A detailed structural analysis verified the combined occupancy of Gd³⁺/Dy³⁺ at the ZrO₂ lattice, while the α-Al₂O₃ component of the composite remains unperturbed. However, the free Gd³⁺ exceeding the substitution limit reacts with Al₂O₃ to yield GdAlO_3. Further, the optimum level of Gd³⁺/Dy³⁺ in ZTA exhibited superior mechanical features with hardness and Young’s modulus of 18 and 251 GPa, respectively. Dy³⁺ presence persuaded emission in the visible region while Gd³⁺/Dy³⁺ combined in ZTA unveiled improved <i>T</i>₁ and <i>T</i>₂ magnetic resonance imaging features with relaxivity values of <i>r</i>₁ = 22 and <i>r</i>₂ = 39 mM^–1 s^–1. In addition, the strong resistance of ZTA against hydrothermal degradation influenced by Gd³⁺/Dy³⁺ combination still adds the material value for further applications

Gadolinium Doping in Zirconia-Toughened Alumina Systems and Their Structural, Mechanical, and Aging Behavior Repercussions

A series of Gd³⁺ dopings in zirconia-toughened alumina (ZTA) systems were undertaken to explore the resultant structural, morphological, hydrothermal aging, and mechanical behavior and imaging contrast abilities. The results from the characterization techniques demonstrate the significance of Gd³⁺ in preserving the structural stability of ZTA systems. ZTA undergoes phase degradation with 10 wt % Gd³⁺ at 1400 °C, while the 100 wt % Gd³⁺ yields GdAlO₃ even at 1200 °C. Gd³⁺ doping at the intermediate level preserves the structural stability of ZTA systems until 1400 °C. Gd³⁺ occupies the ZrO₂ lattice, and its gradual accumulation induces tetragonal ZrO₂ (<i>t</i>-ZrO₂) to cubic ZrO₂ (<i>c</i>-ZrO₂) phase transition. α-Al₂O₃ crystallizes at 1200 °C and remains unperturbed except for its reaction with the free Gd³⁺ ions to yield GdAlO₃. Aging studies and mechanical tests signify the impeccable role of Gd³⁺ in ZTA systems to resist phase degradation. Further, the imaging contrast ability of ZTA systems due to Gd³⁺ doping is verified from the in vitro magnetic resonance imaging (MRI) tests

Unveiling the Co²⁺ Ion Doping-Induced Hierarchical Shape Evolution of ZnO: In Correlation with Magnetic and Photovoltaic Performance

A sustainable, rapid microwave-assisted glycothermal (MW-GT) method has been adopted for the synthesis of pristine ZnO and a series of Zn_1–<i>x</i>Co_<i>x</i>O (<i>x</i> = 0, 0.02, 0.03, 0.05, 0.07, 0.10) within 15 min at 180 °C using ethylene glycol (EG) as solvent. The XRD results reveal that the altering of lattice parameters of ZnO by introduction of Co²⁺ ions and crystalline sizes of Co²⁺ doped ZnO samples decreased with increasing Co²⁺ ion content. A spectacular morphological change of ZnO from well-defined hexagonal prismoid to hierarchical flower-like 1-D nanorods-assembly upon increasing Co²⁺ ion concentration was perceived using FE-SEM and TEM analyses. After Co²⁺ ion inclusion into pristine ZnO, the width of the M–H loop significantly changes, where the diamagnetic behavior of ZnO changes from ferromagnetic to paramagnetic upon further increase in Co²⁺ ion content. Particularly, 5 mol % Co²⁺ ion doped ZnO sample shows enhanced photovoltaic performance in dye-sensitized solar cells (DSSCs) due to nanoscale level intermingling of two different 1-D nanorod-like morphology with particle-like morphology, resulting in size-mismatched combination-induced light-scattering effect, photoinduced charge-carrier formation by charge-transfer transitions of high spin Co²⁺ ions, and lower recombination resistance together with extended electron lifetime, which were deduced from UV–vis and impedance spectroscopy analysis, respectively

Structural, Mechanical, Imaging and in Vitro Evaluation of the Combined Effect of Gd³⁺ and Dy³⁺ in the ZrO₂–SiO₂ Binary System

Mechanical strength and biocompatibility are considered the main prerequisites for materials in total hip replacement or joint prosthesis. Noninvasive surgical procedures are necessary to monitor the performance of a medical device in vivo after implantation. To this aim, simultaneous Gd³⁺ and Dy³⁺ additions to the ZrO₂–SiO₂ binary system were investigated. The results demonstrate the effective role of Gd³⁺ and Dy³⁺ to maintain the structural and mechanical stability of cubic zirconia (<i>c</i>-ZrO₂) up to 1400 °C, through their occupancy of ZrO₂ lattice sites. A gradual tetragonal to cubic zirconia (<i>t</i>-ZrO₂ → <i>c</i>-ZrO₂) phase transition is also observed that is dependent on the Gd³⁺ and Dy³⁺ content in the ZrO₂–SiO₂. The crystallization of either ZrSiO₄ or SiO₂ at elevated temperatures is delayed by the enhanced thermal energy consumed by the excess inclusion of Gd³⁺ and Dy³⁺ at <i>c</i>-ZrO₂ lattice. The addition of Gd³⁺ and Dy³⁺ leads to an increase in the density, elastic modulus, hardness, and toughness above that of unmodified ZrO₂–SiO₂. The multimodal imaging contrast enhancement of the Gd³⁺ and Dy³⁺ combinations were revealed through magnetic resonance imaging and computed tomography contrast imaging tests. Biocompatibility of the Gd³⁺ and Dy³⁺ dual-doped ZrO₂–SiO₂ systems was verified through in vitro biological studies

<i>In Situ</i> Impregnation of Silver Nanoclusters in Microporous Chitosan-PEG Membranes as an Antibacterial and Drug Delivery Percutaneous Device

An <i>in situ</i> synthesis method for preparing silver nanoclusters (AgNCs) embedded in chitosan-polyethylene glycol (CS-PEG) membranes is disclosed. The aim is to develop implantable multifunctional devices for biofilm inhibition and drug release to reduce percutaneous device related complications (PDRCs). A multiple array of characterization techniques confirmed the formation of fluorescent AgNCs with sizes of ∼3 nm uniformly distributed in CS-PEG matrix and their active role in determining the fraction and interconnectivity of the microporous membranes. The presence and increasing contents of AgNCs enhanced the mechanical stability of membranes and decreased their susceptibility to degradation in the presence of lysozyme and H₂O₂. Moreover, the presence and increasing concentrations of AgNCs hindered biofilm formation against Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive) and enabled a sustainable release of an anti-inflammatory drug naproxen <i>in vitro</i> until 24 h. The overall results gathered and reported in this work make the AgNCs impregnated CS-PEG membranes highly promising multifunctional devices combining efficient antibacterial activity and biocompatibility with active local drug delivery