A threefold approach including quantum chemical, molecular docking and molecular dynamic studies to explore the natural compounds from Centaurea jacea as the potential inhibitors for COVID-19

In the current report, we studied the possible inhibitors of COVID-19 from bioactive constituents of Centaurea jacea using a threefold approach consisting of quantum chemical, molecular docking and molecular dynamic techniques. Centaurea jacea is a perennial herb often used in folk medicines of dermatological complaints and fever. Moreover, anticancer, antioxidant, antibacterial and antiviral properties of its bioactive compounds are also reported. The Mpro (Main proteases) was docked with different compounds of Centaurea jacea through molecular docking. All the studied compounds including apigenin, axillarin, Centaureidin, Cirsiliol, Eupatorin and Isokaempferide, show suitable binding affinities to the binding site of SARS-CoV-2 main protease with their binding energies -6.7 kcal/mol, -7.4 kcal/mol, -7.0 kcal/mol, -5.8 kcal/mol, -6.2 kcal/mol and -6.8 kcal/mol, respectively. Among all studied compounds, axillarin was found to have maximum inhibitor efficiency followed by Centaureidin, Isokaempferide, Apigenin, Eupatorin and Cirsiliol. Our results suggested that axillarin binds with the most crucial catalytic residues CYS145 and HIS41 of the Mpro, moreover axillarin shows 5 hydrogen bond interactions and 5 hydrophobic interactions with various residues of Mpro. Furthermore, the molecular dynamic calculations over 60 ns (6×106 femtosecond) time scale also shown significant insights into the binding effects of axillarin with Mpro of SARS-CoV-2 by imitating protein like aqueous environment. From molecular dynamic calculations, the RMSD and RMSF computations indicate the stability and dynamics of the best docked complex in aqueous environment. The ADME properties and toxicity prediction analysis of axillarin also recommended it as safe drug candidate. Further, in vivo and in vitro investigations are essential to ensure the anti SARS-CoV-2 activity of all bioactive compounds particularly axillarin to encourage preventive use of Centaurea jacea against COVID-19 infections.

Effects of Temperature and Grain Size on Diffusivity of Aluminium: Electromigration Experiment and Molecular Dynamic Simulation

Understanding the atomic diffusion features in metallic material is significant to explain the diffusion-controlled physical processes. In this paper, using electromigration experiments and molecular dynamic (MD) simulations, we investigate the effects of grain size and temperature on the self-diffusion of polycrystalline aluminum (Al). The mass transport due to electromigration are accelerated by increasing temperature and decreasing grain size. Magnitudes of effective diffusivity (Deff) and grain boundary diffusivity (DGBs) are experimentally determined, in which the Deff changes as a function of grain size and temperature, but DGBs is independent of the grain size, only affected by the temperature. Moreover, MD simulations of atomic diffusion in polycrystalline Al demonstrate those observations from experiments. Based on MD results, the Arrhenius equation of DGBs and empirical formula of the thickness of grain boundaries at various temperatures are obtained. In total, Deff and DGBs obtained in the present study agree with literature results, and a comprehensive result of diffusivities related to the grain size is presented.

In Silico-Based Discovery of Natural Anthraquinones with Potential against Multidrug-Resistant E. coli

E. coli is a Gram-negative bacterium that causes different human infections. Additionally, it resists common antibiotics due to its outer protective membrane. Natural products have been proven to be efficient antibiotics. However, plant natural products are far less explored in this regard. Accordingly, over 16,000 structures covering almost all African medicinal plants in AfroDb in a structural-based virtual screening were used to find efficient anti-E. coli candidates. These drug-like structures were docked into the active sites of two important molecular targets (i.e., E. coli’s Ddl-B and Gyr-B). The top-scoring hits (i.e., got docking scores < −10 kcal/mol) produced in the initial virtual screening (0.15% of the database structures for Ddl-B and 0.17% of the database structures for Gyr-B in the database) were further refined using molecular dynamic simulation-based binding free energy (ΔG) calculation. Anthraquinones were found to prevail among the retrieved hits. Accordingly, readily available anthraquinone derivatives (10 hits) were selected, prepared, and tested in vitro against Ddl-B, Gyr-B, multidrug-resistant (MDR) E. coli, MRSA, and VRSA. A number of the tested derivatives demonstrated strong micromolar enzyme inhibition and antibacterial activity against E. coli, MRSA, and VRSA, with MIC values ranging from 2 to 64 µg/mL. Moreover, both E. coli’s Ddl-B and Gyr-B were inhibited by emodin and chrysophanol with IC50 values comparable to the reference inhibitors (IC50 = 216 ± 5.6, 236 ± 8.9 and 0.81 ± 0.3, 1.5 ± 0.5 µM for Ddl-B and Gyr-B, respectively). All of the active antibacterial anthraquinone hits showed low to moderate cellular cytotoxicity (CC50 > 50 µM) against human normal fibroblasts (WI-38). Furthermore, molecular dynamic simulation (MDS) experiments were carried out to reveal the binding modes of these inhibitors inside the active site of each enzyme. The findings presented in this study are regarded as a significant step toward developing novel antibacterial agents against MDR strains.