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.     

Deciphering the Role of MicroRNAs in Neuroblastoma

Neuroblastoma (NB) is a type of peripheral sympathetic nervous system cancer that most commonly affects children. It is caused by the improper differentiation of primitive neural crest cells during embryonic development. Although NB occurs for 8% of paediatric cancers, it accounts for 15% of cancer-related deaths. Despite a considerable increase in cytotoxic chemo- and radiotherapy, patients in advanced stages remain virtually incurable. Therefore, there is a desperate necessity for new treatment strategies to be investigated. Accumulating evidence suggested that microRNAs (miRNAs) are a class of non-coding RNAs with 19–25 nucleotides lengths and play a central role in the development of NB carcinogenesis. Fascinatingly, miRNA inhibitors have an antisense property that can inhibit miRNA function and suppress the activity of mature miRNA. However, many studies have addressed miRNA inhibition in the treatment of NB, but their molecular mechanisms and signalling pathways are yet to be analysed. In this study, we impart the current state of knowledge about the role of miRNA inhibition in the aetiology of NB.     

Study of thermal properties of intumescent additive

Bicyclic compounds containing phosphorus on their skeleton such as 2,4,6-trioxa-1-phosphabicyclo[2,2,2]octane-4-methanol phosphate (PEPA) having three active ingredients required for intumescence have been synthesized. The structural characterization of PEPA was carried out by FT-IR, ¹H and ¹³C NMR. The thermal behaviour of the material was studied using TGA, TGA–MS and pyrolysis GC–MS. Thermogravimetric analysis reveals that PEPA undergoes several stages of degradation with a char of about 12% at 800 °C. The TGA–MS studies indicate that the material degrades with the liberation of water, formaldehyde, alkene and alcohols as the major degradation products. Pyrolysis GC–MS results reveal that PEPA isomerizes in the acidic medium. PEPA and/or isomers of PEPA react with formaldehyde, one of the degradation products, to form cross-linked structure and cyclic products with the elimination of water molecule. The thermal degradation mechanisms for PEPA are presented and discussed.     

Effects of electrode voltage,liquid flow rate,and liquid properties on spray chargeability of an air-assisted electrostatic-induction spray-charging system

Combinations of electrode voltage, liquid flow rate, and properties can enhance chargeability of electrostatic sprays for effective pesticide application, though the combined effects of these parameters are not well understood. Generally, 4 kV voltage and lower (30, 45, and 60 mL min^?1) flow rate of tank water produced greater chargeability compared to ground water sprays. The rate of increase in spray chargeability with decreased liquid flow rate was higher in the lower flow rates. The outcome of the study will be helpful for the more targeted and environmentally safe application of pesticide sprays and development of suitable electrostatic spraying systems.     

Observation of strong spin valve effect in bulk Ca3(Ru1-xCrx)2O7

The spin-valve effect is a quantum phenomenon so far only realized in multilayer thin films or heterostructures. Here we report a strong spin-valve effect existing in bulk single crystals of Ca3(Ru1-xCrx)2O7 having an anisotropic, bilayered crystal structure. This discovery opens new avenues to understand the underlying physics of spin valves, and fully realize its potential in practical devices.     

Matrix-assisted laser desorption/ionization mass spectrometry screening for pseudouridine in mixtures of small RNAs by chemical derivatization, RNase digestion and signature products

We have developed a method to screen for pseudouridines in complex mixtures of small RNAs using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). First, the unfractionated crude mixture of tRNAs is digested to completion with an endoribonuclease, such as RNase T1, and the digestion products are examined using MALDI-MS. Individual RNAs are identified by their signature digestion products, which arise through the detection of unique mass values after nuclease digestion. Next, the endonuclease digest is derivatized using N-cyclohexyl-N'-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate (CMCT), which selectively modifies all pseudouridine, thiouridine and 2-methylthio-6-isopentenyladenosine nucleosides. MALDI-MS determination of the CMCT-derivatized endonuclease digest reveals the presence of pseudouridine through a 252 Da mass increase over the underivatized digest. Proof-of-concept experiments were conducted using a mixture of Escherichia coli transfer RNAs and endoribonucleases T1 and A. More than 80% of the expected pseudouridines from this mixture were detected using this screening approach, even on an unfractionated sample of tRNAs. This approach should be particularly useful in the identification of putative pseudouridine synthases through detection of their target RNAs and can provide insight into specific small RNAs that may contain pseudouridine.