Plant-Derived Antiviral Compounds as Potential Entry Inhibitors against Spike Protein of SARS-CoV-2 Wild-Type and Delta Variant: An Integrative in SilicoApproach

The wild-type SARS-CoV-2 has continuously evolved into several variants with increased transmissibility and virulence. The Delta variant which was initially identified in India created a devastating impact throughout the country during the second wave. While the efficacy of the existing vaccines against the latest SARS-CoV-2 variants remains unclear, extensive research is being carried out to develop potential antiviral drugs through approaches like in silico screening and drug-repurposing. This study aimed to conduct the docking-based virtual screening of 50 potential phytochemical compounds against a Spike glycoprotein of the wild-type and the Delta SARS-CoV-2 variant. Subsequently, molecular docking was performed for the five best compounds, such as Lupeol, Betulin, Hypericin, Corilagin, and Geraniin, along with synthetic controls. From the results obtained, it was evident that Lupeol exhibited a remarkable binding affinity towards the wild-type Spike protein (−8.54 kcal/mol), while Betulin showed significant binding interactions with the mutated Spike protein (−8.83 kcal/mol), respectively. The binding energy values of the selected plant compounds were slightly higher than that of the controls. Key hydrogen bonding and hydrophobic interactions of the resulting complexes were visualized, which explained their greater binding affinity against the target proteins—the Delta S protein of SARS-CoV-2, in particular. The lower RMSD, the RMSF values of the complexes and the ligands, Rg, H-bonds, and the binding free energies of the complexes together revealed the stability of the complexes and significant binding affinities of the ligands towards the target proteins. Our study suggests that Lupeol and Betulin could be considered as potential ligands for SARS-CoV-2 spike antagonists. Further experimental validations might provide new insights for the possible antiviral therapeutic interventions of the identified lead compounds and their analogs against COVID-19 infection.     

Inhibitory Effect of Polyphenols from the Whole Green Jackfruit Flour against α-Glucosidase, α-Amylase,Aldose Reductase and Glycation at Multiple Stages and Their Interaction: Inhibition Kinetics and Molecular Simulations

For the first time, α-glucosidase, α-amylase, aldose reductase, and glycation at multiple stages inhibitory assays were used to explore the antidiabetic potential of whole unripe jackfruit (peel with pulp, flake, and seed). Two polyphenols (phenolic acids) with strong antihyperglycaemic activity were isolated from the methanol extract of whole jackfruit flour (MJ) using activity-guided repeated fractionation on a silica gel column chromatography. The bioactive compounds isolated were identified as 3-(3,4-Dihydroxyphenyl)-2-propenoic acid (caffeic acid: CA) and 4-Hydroxy-3,5-dimethoxybenzoic acid (syringic acid: SA) after various physicochemical and spectroscopic investigations. CA (IC₅₀: 8.0 and 26.90 µg/mL) and SA (IC₅₀: 7.5 and 25.25 µg/mL) were identified to inhibit α-glucosidase and α-amylase in a competitive manner with low Ki values. In vitro glycation experiments further revealed that MJ and its components inhibited each stage of protein glycation as well as the generation of intermediate chemicals. Furthermore, CA (IC₅₀: 3.10) and SA (IC₅₀: 3.0 µg/mL) inhibited aldose reductase effectively in a non-competitive manner, respectively. The binding affinity of these substances towards the enzymes examined has been proposed by molecular docking and molecular dynamics simulation studies, which may explain their inhibitory activities. The found potential of MJ in antihyperglycaemic activity via inhibition of α-glucosidase and in antidiabetic action via inhibition of the polyol pathway and protein glycation is more likely to be related to the presence of the phenolic compounds, according to our findings.     

Synthesis,Characterization, and Assessment of Anti-Cancer Potential of ZnO Nanoparticles in an In Vitro Model of Breast Cancer

Advanced innovations for combating variants of aggressive breast cancer and overcoming drug resistance are desired. In cancer treatment, ZnO nanoparticles (NPs) have the capacity to specifically and compellingly activate apoptosis of cancer cells. There is also a pressing need to develop innovative anti-cancer therapeutics, and recent research suggests that ZnO nanoparticles hold great potential. Here, the in vitro chemical effectiveness of ZnO NPs has been tested. Zinc oxide (ZnO) nanoparticles were synthesized using Citrullus colocynthis (L.) Schrad by green methods approach. The generated ZnO was observed to have a hexagonal wurtzite crystal arrangement. The generated nanomaterials were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), UV-visible spectroscopy. The crystallinity of ZnO was reported to be in the range 50–60 nm. The NPs morphology showed a strong absorbance at 374 nm with an estimated gap band of 3.20 eV to 3.32 eV. Microscopy analysis proved the morphology and distribution of the generated nanoparticles to be around 50 nm, with the elemental studies showing the elemental composition of ZnO and further confirming the purity of ZnO NPs. The cytotoxic effect of ZnO NPs was evaluated against wild-type and doxorubicin-resistant MCF-7 and MDA-MB-231 breast cancer cell lines. The results showed the ability of ZnO NPs to inhibit the prefoliation of MCF-7 and MDA-MB-231 prefoliation through the induction of apoptosis without significant differences in both wild-type and resistance to doxorubicin.     

Ion acoustic solitary waves in magnetized electron–positron–ion plasmas with Tsallis distributed electrons

The propagation of ion acoustic (IA) solitary waves is investigated in a magnetized electron-positron-ion (EPI) plasma with Tsalli distributed electrons and Maxwellian positrons. A non-linear Korteweg–de Vries (KdV)-type equation is derived for the potential by using the reductive perturbation method (RPM), and its solitary wave solution is analysed. For a given set of plasma parameters, the present model supports only compressive IA solitary structures. It is found that the variation of various relevant plasma parameters, like the nonextensive parameter q, temperature ratio σ , direction cosine l_z , the positron concentration γ and the magnetic field strength Ω significantly alter the characteristic properties of IA solitary waves.     

Multistage Segmentation of Prostate Cancer Tissues Using Sample Entropy Texture Analysis

In this study, a multistage segmentation technique is proposed that identifies cancerous cells in prostate tissue samples. The benign areas of the tissue are distinguished from the cancerous regions using the texture of glands. The texture is modeled based on wavelet packet features along with sample entropy values. In a multistage segmentation process, the mean-shift algorithm is applied on the pre-processed images to perform a coarse segmentation of the tissue. Wavelet packets are employed in the second stage to obtain fine details of the structured shape of glands. Finally, the texture of the gland is modeled by the sample entropy values, which identifies epithelial regions from stroma patches. Although there are three stages of the proposed algorithm, the computation is fast as wavelet packet features and sample entropy values perform robust modeling for the required regions of interest. A comparative analysis with other state-of-the-art texture segmentation techniques is presented and dice ratios are computed for the comparison. It has been observed that our algorithm not only outperforms other techniques, but, by introducing sample entropy features, identification of cancerous regions of tissues is achieved with 90% classification accuracy, which shows the robustness of the proposed algorithm.     

Collision induced dissociations of non‐derivatized and trimethylsilyl‐derivatized estradiols: similarities in fragmentation patterns

Fragmentation mechanisms of estradiol and trimethylsilyl (TMS)‐derivatized estradiol were studied by triple quadrupole tandem mass spectrometry (MSMS) and density functional theory (DFT) at B3LYP/6‐311G(d,p) level. Collision induced dissociations (CID) of estradiol give product ions that are associated with the cleavage of B, C and D rings. Characteristic fragments from the cleavage of the aromatic ring A were not identified, and this was confirmed with both labeled estradiol and trimethylsilyl (TMS)‐derivatized estradiol. The mechanisms are based on charge‐site directed, radical‐directed and charge remote fragmentations that are consistent with previous studies of steroids. CID spectra show ion pairs at m/z: 145/146, 157/158, 185/186, 211/213 and 225/226 with significant intensities, suggesting that these pairs are not from isotopic contributions. The mechanisms show similarities with some minor differences in the fragmentation patterns between the non‐derivatized and the TMS‐derivatized estradiol. Copyright © 2015 John Wiley & Sons, Ltd.     

Liquid chromatographic separation and determination of aromatic sulfonates in an aquatic environment using a photodiode array and electrospray ionization-mass spectrometer as detectors.

A simple and rapid method involving high-performance liquid chromatographic separation, followed by photodiode array (PDA) and electrospray ionization-mass spectrometric (ESI-MS) detection of aromatic sulfonates in waste-water effluents of industrial units producing optical whitening agents, has been developed. The separation was achieved on a reversed-phase Hypersil C18 column using gradient elution of a mobile phase consisting of 0.05 M ammonium formate-methanol with decreasing concentration of the buffer at room temperature. The minimum detection limits were determined to be in the range of 0.2 - 1.8 x 10(-9) g using PDA and ESI-MS detectors.     

Reduction of clay surface-sorbed organometallics during measurement of X-ray photoelectron spectra (XPS)

Some organometallic compounds, e.g. Ph₃SnCl, react on the surface of the smectite clay, laponite. Other compounds, e.g. Br₃TeC₆H₄CH=NCH₂CH₂N=CHC₆H₄TeBr₃, are sorbed onto the organophilic surface of cetylpyridinium-ion-exchanged Wyoming bentonite. X-ray photoelectron spectroscopy (XPS) is an appropriate technique with which to examine the nature of the surface-sorbed species; however, it is demonstrated that decomposition of the organometallic can occur when the clay surface is exposed over a period of time to energetic X-rays. Thus, care must be taken with the interpretation of data of which some features may be the result of the XPS experiment.     

A novel kinetic determination of nitrite based on the perphenazine-bromate redox reaction

An extremely sensitive and selective kinetic method was developed for the determination of trace levels of nitrite based on its catalytic effect on the oxidation of perphenazine (PPZ) with bromate in a phosphoric acid medium. The reaction rate was monitored spectrophotometrically by tracing the formation of the red-colored oxidized product of PPZ at 525 nm within 30 sec of mixing. The optimum reaction conditions were 4.0 μmol L⁻¹ PPZ, 0.4 mol L⁻¹ H₃PO₄ and 30 mmol L⁻¹ bromate at 25 °C. Using the recommended procedure, nitrite could be determined with a linear calibration graph up to 4.50 ng mL⁻¹ and a detection limit of 0.07 ng mL⁻¹. The method was conveniently applied to the determination of nitrite in samples of rain, polluted well and formulated waste waters. Moreover, the published kinetic spectrophotometric methods for nitrite determination are reviewed.