Molecular Docking and Dynamics Investigations for Identifying Potential Inhibitors of the 3-Chymotrypsin-like Protease of SARS-CoV-2: Repurposing of Approved Pyrimidonic Pharmaceuticals for COVID-19 Treatment

This study demonstrates the inhibitory effect of 42 pyrimidonic pharmaceuticals (PPs) on the 3-chymotrypsin-like protease of SARS-CoV-2 (3CL^pro) through molecular docking, molecular dynamics simulations, and free binding energies by means of molecular mechanics–Poisson Boltzmann surface area (MM-PBSA) and molecular mechanics–generalized Born surface area (MM-GBSA). Of these tested PPs, 11 drugs approved by the US Food and Drug Administration showed an excellent binding affinity to the catalytic residues of 3CL^pro of His41 and Cys145: uracil mustard, cytarabine, floxuridine, trifluridine, stavudine, lamivudine, zalcitabine, telbivudine, tipiracil, citicoline, and uridine triacetate. Their percentage of residues involved in binding at the active sites ranged from 56 to 100, and their binding affinities were in the range from −4.6 ± 0.14 to −7.0 ± 0.19 kcal/mol. The molecular dynamics as determined by a 200 ns simulation run of solvated docked complexes confirmed the stability of PP conformations that bound to the catalytic dyad and the active sites of 3CL^pro. The free energy of binding also demonstrates the stability of the PP–3CL^pro complexes. Citicoline and uridine triacetate showed free binding energies of −25.53 and −7.07 kcal/mol, respectively. Therefore, I recommend that they be repurposed for the fight against COVID-19, following proper experimental and clinical validation.     

Influence of terminal substituent on non-linear S-shaped oligomers consisting of azobenzene moieties at the peripheral arm: Synthesis,characterisation and phase transition behaviour

A series of symmetrical S-shaped mesogens based on 4,4′-bis-(6-bromohexyloxy)biphenyl as a central unit containing two 2-{6-[4-(4-substitutedphenylazo)phenoxy]hexyloxy}phenol as side-chain groups has been successfully synthesised. The terminal substituent was varied from halogen (X = F, Cl, Br and I) to non-halogen (X = C₂H₅ and OC₂H₅). The oligomers with C₂H₅ and OC₂H₅ substituents exhibit predominantly the monotropic nematic (N) phase. The OC₂H₅-containing derivatives possess long-range stability of N phase than its C₂H₅-containing analogue in which it has small range of N phase stability. As for halogen-containing analogues, oligomer with F exhibits monotropic N phase whilst oligomers with Cl and Br exhibit monotropic N and smectic A (SmA) phases. In addition, homologue with Br shows additional phase which is smectic B (SmB) phase upon further cooling. However, the oligomers in which F, Cl and Br were substituted by I exhibits purely monotropic SmA and SmB phases. X-ray diffraction measurements reveal that the smectic phase is inclined to the monolayer structure.     

Application of artificial neural network to evaluation of dimensional accuracy of 3D-printed polylactic acid parts

Additive manufacturing (AM) has begun to replace traditional fabrication because of its advantages, such as easy manufacturing of parts with complex geometry, and mass production. The most important limitation of AM is that dimensional accuracy cannot be achieved in all parts. Dimensional accuracy is essential for high reliability, high performance, and useful final products. This study investigates the impact of printing parameters on the dimensional accuracy of samples fabricated through fused deposition modeling (FDM), an additive manufacturing (AM) method utilizing polylactic acid (PLA) material. The experimental design process was performed using Taguchi methodology. ANOVA was used to determine the most important parameter affecting accuracy. Based on experimental studies, the optimal printing parameters for parts are determined as follows: concentric infill pattern, 3 mm wall thickness, 70% infill density, and a layer thickness of 200 μm. Artificial neural network (ANN) was used in the evaluation and prediction of the results. The R-square (R²) performance evaluation criterion was above 95% from the ANN results. This value shows that the results are significant. The data acquired from this study may assist in identifying optimal parameters that contribute to the fabrication of samples with high dimensional accuracy using the FDM method.     

New nonautonomous combined multi-wave solutions for ( $$\varvec{2+1}$$ 2 + 1 )-dimensional variable coefficients KdV equation

Nonlinear Dynamics - A variety of new types of nonautonomous combined multi-wave solutions of the ( $$2+1$$ )-dimensional variable coefficients KdV equation is derived by means of the generalized...     

Spectrometric studies on the cloud points of Triton X-405

The effect of various chemicals on the cloud point (CP) of nonionic surfactant Triton X-405 (TX-405) in aqueous solutions has been investigated. In the measurements of cloud point temperatures, UV–visible spectrophotometer was used instead of visual observation. The values of CP for Triton X-405 could not be measured directly because TX-405 had an average number of oxyethylene units per molecule, p ≈ 35 and a CP > 100 °C. To avoid additional measurements under pressure, TX-405 had their CP lowered below the normal boiling point of their solutions by adding the salting-out, CP-lowering salts at various concentrations, measuring the depressed CP values and extrapolating them to zero salt concentration. The CP values decrease linearly with increasing concentration of salts at studied concentrations. The results showed that the addition of the simple salts and nonionic surfactant Triton X-114 (TX-114) which are infinitely miscible with water decreased the cloud point of the TX-405. In this study, the real CP values of TX-405 which are merely listed as >100 °C in the literature was found as 116 ± 1 °C in various samples. In the lyotropic series, it is expected that the effect of F⁻ > Cl⁻ > Br⁻ will be on the decrease in CP, because the ionic sizes increase along the group consequently decreasing the formal charge density on anion, thus lowering the attraction on anion and thereby lowering the attraction of water. The order of CP depression for the other anions is as follows: PO₄³⁻ > SO₄²⁻ > NO₃⁻ > Br⁻. This means that electrolyte containing trivalent anions is more effective at salting-out the PEO chain than those containing divalent anions and monovalent anions. Cations effectiveness is present in the following order for change: Na⁺ > K⁺ > NH₄⁺ because of their effect on water structure and their hydrophilicity. Overall the electrolytes and nonelectrolytes have a large amount of effect on CP of nonionic surfactant, because of their effect on water structure and their hydrophilicity.     

Synthesis and characterizations of N,N,N′,N′-tetrakis (diphenylphosphino)ethylendiamine derivatives: Use of palladium(II) complex as pre-catalyst in Suzuki coupling and Heck reactions

Oxidation of N,N,N′,N′-tetrakis(diphenylphosphino)ethylendiamine (1) with elemental sulfur and selenium gives the corresponding sulfide and selenide, respectively, [(Ph₂P(E))₂NCH₂CH₂N(P(E)Ph₂)₂] (E: S 1a, Se 1b). Complexes of 1 [(M₂Cl₄){(Ph₂P)₂NCH₂CH₂N(PPh₂)₂}] (M: Ni(II) 1c, Pd(II) 1d, Pt(II) 1e) were prepared by the reaction of 1 with NiCl₂ or [MCl₂(COD)] (M = Pd, Pt). The new compounds were characterized by NMR, IR spectroscopy and elemental analysis. The catalytic activity of Pd(II) complex 1d was tested in the Suzuki coupling reaction and Heck reaction. The palladium complex 1d catalyses the Heck reaction between styrene and aryl bromides as well as Suzuki coupling reaction between phenylboronic acid and arylbromides affording stilbenes and biphenyls in high yield, respectively.     

A variable neighbourhood search algorithm for the open vehicle routing problem

In the open vehicle routing problem (OVRP), the objective is to minimise the number of vehicles and then minimise the total distance (or time) travelled. Each route starts at the depot and ends at a customer, visiting a number of customers, each once, en route, without returning to the depot. The demand of each customer must be completely fulfilled by a single vehicle. The total demand serviced by each vehicle must not exceed vehicle capacity. Additionally, in one variant of the problem, the travel time of each vehicle should not exceed an upper limit.     

Artifact-free black-blood cine cardiac imaging in a single breath-hold

Fast imaging using the STimulated Echo Acquisition Mode (STEAM) sequence can produce cine images of the heart with black-blood contrast. Nevertheless, correction of deformation-related artifacts is required in order to maintain myocardial signal throughout the cardiac cycle. Recent work by our group has eliminated this artifact by combining two STEAM sequences acquired with two different demodulation gradients. Unfortunately, these two STEAM sequences were acquired on two separate breath-holds; thus, scan time doubled. In this work, we present a technique to reduce the total scan time by one half, without sacrificing image quality. The technique is based on interleaving two demodulations within one acquisition in order to obtain quality cine images of the heart in a single breath-hold. The technique was tested on animal models and human subjects, and the impact of interleaved acquisition on image quality was studied using quantitative and qualitative measures.     

Multicritical behaviors of the antiferromagnetic Blume–Emery–Griffiths model with the external magnetic field on the Bethe lattice

The antiferromagnetic Blume–Emery–Griffiths model in an external magnetic field is studied by using the exact recursion relations on the Bethe lattice for arbitrary values of biquadratic and for negative values of bilinear interactions. We have studied the thermal variations of two-sublattice magnetizations belonging to spin-1 BEG model to obtain the phase diagrams on the (H/|J|,kT/|J|)$(H/|J|,\mathit{kT}/|J|)$ plane. As a result, we have found that the system presents second- and first-order phase transitions, therefore, tricritical points for appropriate values of K/|J|$K/\left|J\right|$, D/|J|$D/\left|J\right|$ and q  . We have also found that the second-order phase transition lines exhibit reentrant phenomena in temperature, besides it also shows reentrant phenomena for the first-order phase lines in external magnetic field for q=4$q=4$ and 6.     

Unsteady MHD double-diffusive convection boundary-layer flow past a radiate hot vertical surface in porous media in the presence of chemical reaction and heat sink

This paper presents an analytical study of the unsteady MHD free convective heat and mass transfer flow of a viscous, incompressible, gray, absorbing-emitting but non-scattering, optically-thick and electrically conducting fluid occupying a semi-infinite porous regime adjacent to an infinite moving hot vertical plate with constant velocity. We employ a Darcian viscous flow model for the porous medium the Rosseland diffusion approximation is used to describe the radiative heat flux in the energy equation. The homogeneous chemical reaction of first order is accounted in mass diffusion equation. The governing equations are solved in closed form by Laplace-transform technique. A parametric study of all involved parameters is conducted and representative set of numerical results for the velocity, temperature, concentration, shear stress function $\frac{\partial u}{\partial y} \vert_{y=0}$ , temperature gradient $\frac{\partial \theta }{ \partial y}\vert_{y=0}$ , and concentration gradient $\frac{ \partial \phi }{\partial y}\vert_{y=0}$ is illustrated graphically and physical aspects of the problem are discussed.