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The primary aim of the current investigation is to contribute to SARS-CoV-2 research by identifying potential lead compounds for clinical applications, with a specific focus on inhibitors targeting the main protease (Mpro). In this research, molecular docking analysis was conducted using the software molecular operating environmental (MOE) to evaluate the potency of bioactive compounds sourced from medicinal plants as inhibitors of SARS- -CoV-2 Mpro. Among 118 natural compounds with anti-HIV characteristics, the top seven candidates (h3, h84, h85, h87, h90, h108 and h110), were identified based on their superior binding energies with comparison to the reference ligand N3. These selected compounds exhibited binding affinities of –33.996, –35.336, –32.615, –32.154, –33.452, –31.903 and –40.360 kJ mol-1, respectively. To further refine our shortlist of potential candidates for human application, we examined the drug-likeness, and the pharmaceutical attributes of these compounds using the SwissADME web server. Among them, only two compounds, namely h85 and h87, demonstrated favorable pharmacological properties suitable for human administration. These two compounds were subsequently shortlisted for further investigation. To explore the conformational stability of ligands within the Mpro active site, we performed molecular dynamics (MD) simulations. These simulations showed reliable and steady trajectories, supported by analyses of root-mean-square-fluctuation (RMSF) and root- -mean-square deviation (RMSD). These findings and favorable molecular properties as well as interaction profiles suggest that these two lead compounds may be promising SARS-CoV-2 therapeutic candidates. They present exciting starting points for further drug design.

This paper reports a detailed numerical investigation on the buckling aspects of laminated composite shell panels of three forms (cylindrical, spherical and hyperbolic paraboloid) with five support conditions exposed to linearly varying in-plane edge load employing eight nodded isoparametric finite element formulation. The impacts of different parameters including ply orientation, load factor, shell forms, aspect ratio, modulus ratio, curvature ratio, width-to-thickness ratio and angle of lamination on the buckling load of shell panels are examined. It is found that the various parameters addressed in this study have a remarkable impact on the buckling phenomena of laminated composite shell panels. Further, a comparison is made showing the effects of five types of compressive edge loads like uniform, triangular, parabolic, partial edge load and point load on the buckling phenomena of laminated shell panels with respect to five support conditions. [ABSTRACT FROM AUTHOR]

For the binary mixture of water and N, N-dimethylacetamide (DMA), observations have been done of the ultrasonic velocity (u), density (ρ), viscosity (η) and refractive index (n) in excess of the whole composition range at various temperature. Deviation in ultrasonic velocity (Δu), excess intermolecular free length (LfE), excess acoustic impedance (ZE), excess molar volume (VmE), deviation in molar refraction (ΔRm), deviation in viscosity (Δη) and excess Gibbs' free energy of activation for viscous flow (ΔG*E) were used to investigate the intermolecular interactions present in the mixture. Derived parameters such as isoentropic compressibility (Ks), the specific heat ratio (γ), and the effective Debye temperature (qD) at varying concentrations of DMA have also been computed using experimental data. Various semi-empirical mixing rules have also been applied to the binary mixture. Density functional theory is utilised to optimise the geometry of DMA, DMA with water, and calculation of H-bonded intermolecular interactions. [ABSTRACT FROM AUTHOR]

We report the synthesis, spectroscopic properties, and anti-proliferative efficacy of the adamantane-linked 1,2,4-triazole derivative 5-(adamantan-1-yl)-4-(3-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione. Crystal packing and intermolecular interactions have been quantified using Hirshfeld surfaces and two-dimensional fingerprint plots. ADMET characteristics, bioavailability, and drug-likeness define the compound's bioactivity. The gastrointestinal absorption is anticipated to be high, and the projected bioavailability score is 0.55. The topological polar surface area and iLOGP, XLOGP, WLOGP, and MLOGP lipophilicity parameters have been calculated to be 65.70 Å2, 3.24, 4.74, 5.05, and 4.07, respectively. To investigate 5A4ClT's EGFR inhibition and its use in the treatment of non-small cell lung cancer, Autodock Vina was used to dock it with the crystal structure of the EGFR kinase domain protein. The title chemical hydrophobically interacts with the receptor residues LEU718, VAL726, ALA743, GLU762, THR790, LEU792, MET793, GLY796, ARG841, ASN842, and LEU844 and forms hydrogen bonds with ASP855 and THR854 with an affinity of −8.3 kcal/mol. Toxicity end points and comparison with NSCLC drugs yielded promising findings. 120 ns molecular dynamics simulations confirmed the ligand's dynamic stability in the target protein's binding pocket. This research lays the groundwork for future in vivo investigations of 5A4ClT as a non-small cell lung cancer therapy. [ABSTRACT FROM AUTHOR]

Huperzine A (HUP) plays a crucial role in Alzheimer's therapy by enhancing cognitive function through increased cholinergic activity as a reversible acetylcholinesterase (AChE) inhibitor. Despite some limitations being seen in AChE inhibitors, ongoing research remains dedicated to finding innovative and more effective treatments for Alzheimer's disease. To achieve the goal of the discovery of potential HUP analogues with improved physicochemical properties, less toxic properties, and high biological activity, many in silico methods were applied. Based on the acetylcholinesterase–ligand complex, an e-pharmacophore model was developed. Subsequently, a virtual screening involving a collection of 1762 natural compounds, sourced from the PubChem database, was performed. This screening yielded 131 compounds that exhibited compatibility with the established pharmacophoric hypothesis. These selected ligands were then subjected to molecular docking within the active site of the 4EY5 receptor. As a result, we identified four compounds that displayed remarkable docking scores and exhibited low free binding energy to the target. These top four compounds, CID_162895946, CID_44461278, CID_44285285, and CID_81108419, were submitted to ADMET prediction and molecular dynamic simulations, yielding encouraging findings in terms of their pharmacokinetic characteristics and stability. Finally, the molecular dynamic simulation, cross-dynamic correlation matrix, free energy landscape, and MM-PBSA calculations demonstrated that two ligands from the selected ligands formed very resilient complexes with the enzyme acetylcholinesterase, with significant binding affinity. Therefore, these two compounds are recommended for further experimental research as possible (AChE) inhibitors. [ABSTRACT FROM AUTHOR]

The adsorption reaction of adenine as a purine nucleobase on the surface of the nano-SiO2 cluster was investigated using density functional theory (DFT) calculations. Adsorption energies, interaction distances, dipole moments, thermochemical parameters, NCI analysis, electron localization function (ELF), and FTIR spectra are calculated to deeply understand the impact of adenine adsorption on the electronic and chemical properties of the nano-SiO2 cluster. Different configurations were investigated for the adsorption of adenine to examine the nano-bio interface via the interaction with various sites present on biomolecules designated as –N1, –N2, –N3, –NH2, and –NCN. Adsorption energies for the different adenine sites ranged from − 1.45 to 4.19 eV. Based on the change in adsorption energies (Ead), free energies (ΔG), and the NCI analysis and ELF, the interaction of adenine nucleobase via –N2 was found to be essential for thermodynamically stable and energetically favorable states. The density of states analysis (DOS) also revealed the prominent interactions of the biomolecules with the nano-SiO2 cluster. The decrease in HOMO–LUMO band gaps on the adsorption of the biomolecules was a pertinent phenomenon, demonstrating the substantial chemical reactions between the biomolecules and the nano-SiO2 clusters. [ABSTRACT FROM AUTHOR]