In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike Protein

Despite ongoing vaccination programs against COVID-19 around the world, cases of infection are still rising with new variants. This infers that an effective antiviral drug against COVID-19 is crucial along with vaccinations to decrease cases. A potential target of such antivirals could be the membrane components of the causative pathogen, SARS-CoV-2, for instance spike (S) protein. In our research, we have deployed in vitro screening of crude extracts of seven ethnomedicinal plants against the spike receptor-binding domain (S1-RBD) of SARS-CoV-2 using an enzyme-linked immunosorbent assay (ELISA). Following encouraging in vitro results for Tinospora cordifolia, in silico studies were conducted for the 14 reported antiviral secondary metabolites isolated from T. cordifolia—a species widely cultivated and used as an antiviral drug in the Himalayan country of Nepal—using Genetic Optimization for Ligand Docking (GOLD), Molecular Operating Environment (MOE), and BIOVIA Discovery Studio. The molecular docking and binding energy study revealed that cordifolioside-A had a higher binding affinity and was the most effective in binding to the competitive site of the spike protein. Molecular dynamics (MD) simulation studies using GROMACS 5.4.1 further assayed the interaction between the potent compound and binding sites of the spike protein. It revealed that cordifolioside-A demonstrated better binding affinity and stability, and resulted in a conformational change in S1-RBD, hence hindering the activities of the protein. In addition, ADMET analysis of the secondary metabolites from T. cordifolia revealed promising pharmacokinetic properties. Our study thus recommends that certain secondary metabolites of T. cordifolia are possible medicinal candidates against SARS-CoV-2.     

Electron Paramagnetic Resonance of VO2+ in M2Zn(SeO4)2 · 6H2O(M=K,Rb) Single Crystals

The EPR spectrum of VO²⁺ has been studied in single crystals of K₂Zn(SeO₄)₂ · 6H₂O and Rb₂Zn(SeO₄)₂ ∼ 6H₂O at ∼9.45 GHz. VO²⁺ substitutes for Zn²⁺ have preferential orientations in the lattice. The V = O of the intense vanadyl center is nearly along the longest Zn H₂O direction. Spin-Hamiltonian parameters have been evaluated from single crystal as well as from powder spectra.     

Synthesis and antimicrobial activities of isomers of N(4),N(11)-dimethyl-3,5,7,7,10,12,14,14-octamethyl-1,4,8,11-tetraazacyclotetradecane and their nickel(II) complexes

The reactions of two isomers of 3,5,7,7,10,12,14,14-octamethyl-1,4,8,11-tetraazacyclotetradecane (differing in the orientation of the methyl groups on the chiral carbon atoms), designated as L(B) and L(C), with CH(3)I in the ratio of 1:4 resulted in the substitution of the N(4) and N(11) protons by CH(3) groups, forming the dimethyl derivatives L(BZ) and L(CZ), respectively. These ligands, on interaction with nickel(II) acetate tetrahydrate and subsequent addition of lithium perchlorate, produce square-planar yellow [NiL(BZ)][ClO(4)](2) and orange [NiL(C'Z)][ClO(4)](2). These nickel complexes undergo axial ligand addition reactions with NCS(-), Cl(-), Br(-), and I(-) as X(-) to form six-coordinate trans-diisothiocyanato, -dichloro, -dibromo, and -diiodo complexes of formula [NiLX(2)], where L = L(BZ) or L(C'Z), and X = SCN, Cl, Br, or I. All these compounds have been characterized on the basis of analytical, spectroscopic, conductometric, and magnetochemical data. The structures of L(BZ) and two variants of [Ni"L(BZ)"][ClO(4)](2) (crystallizing in the space group P2(1)/n and Pn, respectively; "L(BZ)" symbolizes partially methylated ligand) have been determined by single-crystal X-ray analyses. The antifungal and antibacterial activities of these compounds have been studied against some phytopathogenic fungi and bacteria.     

Structure,optical and magnetic properties of LaFeO3 nanoparticles prepared by polymerized complex method

This work reports the study the structure, optical and magnetic properties of LaFeO₃ nanoparticles synthesized by the polymerized complex method. The LaFeO₃ nanoparticles were successfully obtained from calcination of the precursor at different temperatures from 750 to 1,050 °C in air for 2 h. The calcined LaFeO₃ nanoparticles were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), UV–Visible spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray absorption near edge spectroscopy (XANES) and vibrating sample magnetometry. The XRD and TEM results showed that all LaFeO₃ samples had a single phase nature with the orthorhombic structure. The estimated crystallite sizes were in the range of 44.5 ± 2.4–74.1 ± 4.9 nm. UV–Vis spectra showed strong UV and Vis absorption with small band gap energy. The valence states of Fe ions were in the Fe³⁺ and Fe⁴⁺ state, as confirmed by XPS and XANES results. The weak ferromagnetic behavior with specific saturation magnetization of 0.1 emu/g at 10 kOe was obtained for the small particle of 44.5 ± 2.4 nm. The uncompensated spins at the surface was proposed as playing a part in the magnetic properties of small sized LaFeO₃.     

Kinetics of oxidation of ethanol by acid bromate

The kinetics of oxidation of ethanol by bromate ion in hydrochloric acid medium has been investigated. The reaction involves the formation of the intermediate bromate ester which is facilitated by the methyl group in ethanol but the electron attracting character (F>Cl>Br) of the halogens attached to the -carbon of the alcohol makes the esterification more difficult.

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A rapid method for detection of cell adhesion molecules (CAMs) on human umbilical vein endothelial cells (HUVECs)

Detection of cell surface proteins is widely used as molecular markers for initiation, progression and severity of many diseases. In particular, detection of cell adhesion molecules (CAMs) on endothelial cells is important as it indicates the extent of inflammation associated with several diseases including arthritis, asthma, tumor metastasis, etc. Here, we report, a rapid method for detection of CAMs on endothelial cells by covalently immobilizing TNF-α induced cells on a photoactivated polystyrene microtiter plate at 50 °C in 45 min followed by performing enzyme-linked immunosorbent assay (ELISA) technique at elevated temperature. Our method reduced the time of cell-ELISA to 3 h with results akin to conventional cell-ELISA carried out in 38 h. The method thus described herein could be potentially useful in clinical and research laboratories for rapid detection of cell surface proteins including CAMs on intact cell samples.     

Prudent Practices in ex situ Durability Analysis Using Cyclic Voltammetry for Platinum-based Electrocatalysts

Platinum (Pt)-based electrocatalysts are at the vanguard of research initiatives to meet activity and durability targets for promoting large-scale adoption of fuel cell vehicles. Ex situ characterization of electrocatalyst activity and durability using cyclic voltammetry (CV) has a steep learning curve. Thus, many researchers who do not receive formal training in electrochemistry are left unsure how to proceed. Herein, we identify and compile prudent practices for reliable assessment of ECSA values with examples from our research on nanoscale catalytic films formed by the self-terminating electrodeposition of Pt. Starting with a conceptual framework to understand typical features in the CV of reversible redox couples, we present prudent practices in acquiring CV data aimed at nonelectrochemists. We then highlight specific features related to ECSA computation from Pt CV. Finally, we suggest safeguards that help avoid missteps and achieve repeatable results while conducting ex situ durability tests that extend over days.     

Reliable Functionalization of 5,6-Fused Bicyclic N-Heterocycles Pyrazolopyrimidines and Imidazopyridazines via Zinc and Magnesium Organometallics

DFT-calculations allow prediction of the reactivity of uncommon N-heterocyclic scaffolds of pyrazolo[1,5-a]pyrimidines and imidazo[1,2-b]pyridazines and considerably facilitate their functionalization. The derivatization of these N-heterocycles was realized using Grignard reagents for nucleophilic additions to 5-chloropyrazolo[1,5-a]pyrimidines and TMP₂Zn ⋅ 2 MgCl₂ ⋅ 2 LiCl allowed regioselective zincations. In the case of 6-chloroimidazo[1,2-b]pyridazine, bases such as TMP₂Zn ⋅ MgCl₂ ⋅ 2 LiCl, in the presence or absence of BF₃ ⋅ OEt₂, led to regioselective metalations at positions 3 or 8. Subsequent functionalizations were achieved with TMPMgCl ⋅ LiCl, producing various polysubstituted derivatives (up to penta-substitution). X-ray analysis confirmed the regioselectivity for key functional heterocycles.