Virtual Screening of Artemisia annua Phytochemicals as Potential Inhibitors of SARS-CoV-2 Main Protease Enzyme

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human coronaviruses that emerged in China at Wuhan city, Hubei province during December 2019. Subsequently, SARS-CoV-2 has spread worldwide and caused millions of deaths around the globe. Several compounds and vaccines have been proposed to tackle this crisis. Novel recommended in silico approaches have been commonly used to screen for specific SARS-CoV-2 inhibitors of different types. Herein, the phytochemicals of Pakistani medicinal plants (especially Artemisia annua) were virtually screened to identify potential inhibitors of the SARS-CoV-2 main protease enzyme. The X-ray crystal structure of the main protease of SARS-CoV-2 with an N3 inhibitor was obtained from the protein data bank while A. annua phytochemicals were retrieved from different drug databases. The docking technique was carried out to assess the binding efficacy of the retrieved phytochemicals; the docking results revealed that several phytochemicals have potential to inhibit the SARS-CoV-2 main protease enzyme. Among the total docked compounds, the top-10 docked complexes were considered for further study and evaluated for their physiochemical and pharmacokinetic properties. The top-3 docked complexes with the best binding energies were as follows: the top-1 docked complex with a −7 kcal/mol binding energy score, the top-2 docked complex with a −6.9 kcal/mol binding energy score, and the top-3 docked complex with a −6.8 kcal/mol binding energy score. These complexes were subjected to a molecular dynamic simulation analysis for further validation to check the dynamic behavior of the selected top-complexes. During the whole simulation time, no major changes were observed in the docked complexes, which indicated complex stability. Additionally, the free binding energies for the selected docked complexes were also estimated via the MM-GB/PBSA approach, and the results revealed that the total delta energies of MMGBSA were −24.23 kcal/mol, −26.38 kcal/mol, and −25 kcal/mol for top-1, top-2, and top-3, respectively. MMPBSA calculated the delta total energy as −17.23 kcal/mol (top-1 complex), −24.75 kcal/mol (top-2 complex), and −24.86 kcal/mol (top-3 complex). This study explored in silico screened phytochemicals against the main protease of the SARS-CoV-2 virus; however, the findings require an experimentally based study to further validate the obtained results.     

Effect of ZnO Nanofiller on Structural and Electrochemical Performance Improvement of Solid Polymer Electrolytes Based on Polyvinyl Alcohol–Cellulose Acetate–Potassium Carbonate Composites

In this study, a solution casting method was used to prepare solid polymer electrolytes (SPEs) based on a polymer blend comprising polyvinyl alcohol (PVA), cellulose acetate (CA), and potassium carbonate (K₂CO₃) as a conducting salt, and zinc oxide nanoparticles (ZnO-NPs) as a nanofiller. The prepared electrolytes were physicochemically and electrochemically characterized, and their semi-crystalline nature was established using XRD and FESEM. The addition of ZnO to the polymer–salt combination resulted in a substantial increase in ionic conductivity, which was investigated using impedance analysis. The size of the semicircles in the Cole–Cole plots shrank as the amount of nanofiller increased, showing a decrease in bulk resistance that might be ascribed to an increase in ions due to the strong action of the ZnO-NPs. The sample with 10 wt % ZnO-NPs was found to produce the highest ionic conductivity, potential window, and lowest activation energy (E_a) of 3.70 × 10^–3 Scm^–1, 3.24 V, and 6.08 × 10^–4 eV, respectively. The temperature–frequency dependence of conductivity was found to approximately follow the Arrhenius model, which established that the electrolytes in this study are thermally activated. Hence, it can be concluded that, based on the improved conductivity observed, SPEs based on a PVA-CA-K₂CO₃/ZnO-NPs composite could be applicable in all-solid-state energy storage devices.     

Necessary and sufficient conditions for oscillation of second‐order dynamic equations on time scales

In this paper, we establish necessary and sufficient conditions for oscillation of second‐order strongly superlinear and strongly sublinear dynamic equations. Our results unify and improve many known results in the literature.     

Spectrophotometric determination of acetone in acetic acid

A sensitive and selective spectrophotometric method for the determination of acetone in acetic acid has been worked out. It is based on the reaction of acetone with diazotized p-aminobenzoic acid in a strongly alkaline medium to form a purple color with maximum absorption at 540 nm. Beer's law holds up in the range 20–140 μg of acetone in a final volume of 20 ml, with a molar absorptivity of 8.1 × 10³ liters mol^?1 cm^?1, sensitivity index of 0.0072 μg cm^?2, relative error of ?1.9 to +0.6%, and relative standard deviation of 0.7–3.5, depending on the concentration level. Furthermore, the color reaction is fast, and the procedure is simple, and avoids the use of an extraction.     

Matrix-assisted laser desorption/ionization mass spectrometry with re-engineered 2,5-dihydroxybenzoic acid derivative

Dihydroxybenzoic acid was modified to three analogues (M2, M4 and M6). The analogues exhibited specific properties that resulted in enhancement of analyte signal intensity with or without addition of iodine compared to the underivatized parent. Addition of iodine to M2, an ester of dihydroxybenzoic acid that had a terminal double bond in the alkyl chain, resulted in peak intensities comparable to the parent, indicating that iodine interaction across the double bond resulted in enhancement although the exact mechanism is not fully understood. No enhancement on addition of iodine was observed for M4, which had a long alkyl chain that contained no double bonds. The alkyl chain allowed micelle formation in solution, which in turn allowed more uniform analyte-to-matrix mixing. The final analogue combined the long alkyl chain of M4 with the double bond of M2 and exhibited either similar peak intensities to that of dihydroxybenzoic acid or better. Micelle formation in solution was examined using spectroscopy and in the solid by reflective microscopy. The standard deviation from spot to spot was considerably lower relative to dihydroxybenzoic acid (RSD 3.4%vs. 14.2%). Unlike dihydroxybenzoic acid, the novel matrix M6 was able to yield characteristic peaks for analytes such as ubiquitin.     

Use of Enzymatic Digestion and Chemical Methylation Followed by Matrix-assisted Laser Desorption/Ionisation (MALDI) Mass Spectrometry to Sequence a 60kDa Commercial Fraction of Cellulose Acetate

Cellulose acetate was characterized by using enzyme in both digestion and chemical derivation and acetolysis. The fragments were normalised and compared on an anhydroglucose scale, using mass spectrometry to identify the different sized fragments. It was determined that at least two sub-populations for cellulose acetate existed within the parent. The macroscopic effect of this variation in the degree of acetylation will be a modification of the structural properties of the polymer chains. It was found that through comparison with enzyme-based degradation, an estimation of the acetylation topography of the cellulose acetate fraction could be made. Enzyme degradation produced a number of oligosaccharides of more than 10 glucose units, presumably resistant to enzyme degradation because they contained acetate groups. Chemical hydrolysis gave a random ladder of short sequences of mainly 3–4 glucose units some of which had a high methyl ether content, that were analysed by mass and converted to an anhydroglucose mass scale. This approach could be used to demonstrate differences between large biopolymers of cellulose acetate that previously gave an overall average rather than a specific ladder average.     

Instability criteria for impulsive hybrid state dependent delay integrodifferential systems

In this paper, we present the sufficient conditions ensuring the instability of the zero solution of an impulsive state dependent delay integrodifferential system for different conditions on the delay function. We assume the instability of the associated linear impulsive system and apply the idea of dichotomies together with Schauder–Tychonoff theorem to establish the sufficient conditions for the unstable solution of the problem.