Identification of Potential Binding Sites of Sialic Acids on the RBD Domain of SARS-CoV-2 Spike Protein

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still an emergent pandemic for humans. The virus infection is achieved by penetrating its spike protein to host cells via binding with ACE2. Moreover, recent studies show that SARS-CoV-2 may have multiple receptors that need to be further revealed. SARS-CoV-2 shares similar sequences of the spike protein with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which can invade host cells by binding to either DPP4 or sialic acids. Sialic acids can be linked to the terminal of glycoproteins and gangliosides are used as one of the receptors of many types of viruses. Therefore, it is very interesting to determine whether sialic acid is a potential receptor of SARS-CoV-2. To address this question, we took N-Acetylneuraminic acid (Neu5Ac), a type of predominant sialic acid found in human cells, as the molecular probe to computationally search the surface of the spike protein to locate the potential binding sites of Neu5Ac. SPR analysis and mass spectrum analysis confirmed the interaction between Neu5Ac and spike protein. This study shows that sialic acids can moderately interact with the spike protein of SARS-CoV-2 by binding between the two RBDs of the spike protein, indicating it could be a potential secondary or auxiliary receptor of SARS-CoV-2.

A New Thiazinedione Glycoside From the Fruits of Xanthium strumarium L.

A total of 4 thiazinedione derivatives including 1 new thiazinedione glycoside (1) and 3 known compounds (2-4) were isolated from the fruits of Xanthium strumarium L. Their chemical structures were determined as 7-hydroxymethyl-8,8-dimethyl-4,8-dihydrobenzo[1,4]-thiazine-3,5-dione-11- O-[ β-D-glucopyranosyl-(1→6)- O-β-D-glucopyranoside] (1), 7-hydroxymethyl-8,8-dimethyl-4,8-dihydrobenzo[1,4]-thiazine-3,5-dione-11- O-[ β-D-apiofuranosyl-(1→6)- O- β-D-glucopyranoside] (2), xanthiside (3), and xanthiazone (4) by extensive nuclear magnetic resonance spectroscopic and high-resolution electron spray ionization mass spectrum analysis and by comparison of the spectral data with those reported in the literature. Compounds 3 and 4 exhibited cytotoxic activity against lung carcinoma (SK-LU-1), human breast carcinoma (MCF-7), hepatocellular carcinoma (HepG2), and skin melanoma (SK-Mel-2) cell lines with half-maximal inhibitory concentration (IC50) values ranging from 27.0 ± 1.1 to 43.2 ± 1.8 µM.

ClipsMS: An Algorithm for Analyzing Internal Fragments Resulting from Top-Down Mass Spectrometry

<p>Here we describe ClipsMS, an algorithm that can assign both terminal and internal fragments generated by top-down MS fragmentation. Further, ClipsMS can be used to locate various modifications on the protein sequence. Using ClipsMS to assign TD-MS generated product ions, we demonstrate that for apo-myoglobin, the inclusion of internal fragments increases the sequence coverage up to 78%. Interestingly, many internal fragments cover complimentary regions to the terminal fragments that enhance the information that is extracted from a single top-down mass spectrum. Analysis of oxidized apo-myoglobin using terminal and internal fragment matching by ClipsMS confirmed the locations of oxidation sites on the two methionine residues. Internal fragments can be beneficial for top-down protein fragmentation analysis, and ClipsMS can be a valuable tool for assigning both terminal and internal fragments present in a top-down mass spectrum.</p>

ClipsMS: An Algorithm for Analyzing Internal Fragments Resulting from Top-Down Mass Spectrometry

<p>Here we describe ClipsMS, an algorithm that can assign both terminal and internal fragments generated by top-down MS fragmentation. Further, ClipsMS can be used to locate various modifications on the protein sequence. Using ClipsMS to assign TD-MS generated product ions, we demonstrate that for apo-myoglobin, the inclusion of internal fragments increases the sequence coverage up to 78%. Interestingly, many internal fragments cover complimentary regions to the terminal fragments that enhance the information that is extracted from a single top-down mass spectrum. Analysis of oxidized apo-myoglobin using terminal and internal fragment matching by ClipsMS confirmed the locations of oxidation sites on the two methionine residues. Internal fragments can be beneficial for top-down protein fragmentation analysis, and ClipsMS can be a valuable tool for assigning both terminal and internal fragments present in a top-down mass spectrum.</p>

Bioremediation of Explosive TNT by Trichoderma viride

Nitroaromatic and nitroamine compounds such as 2,4,6-trinitrotoluene (TNT) are teratogenic, cytotoxic, and may cause cellular mutations in humans, animals, plants, and microorganisms. Microbial-based bioremediation technologies have been shown to offer several advantages against the cellular toxicity of nitro-organic compounds. Thus, the current study was designed to evaluate the ability of Trichoderma viride to degrade nitrogenous explosives, such as TNT, by microbiological assay and Gas chromatography–mass spectrometry (GC–MS) analysis. In this study, T. viride fungus was shown to have the ability to decompose, and TNT explosives were used at doses of 50 and 100 ppm on the respective growth media as a nitrogenous source needed for normal growth. The GC/MS analysis confirmed the biodegradable efficiency of TNT, whereas the initial retention peak of the TNT compounds disappeared, and another two peaks appeared at the retention times of 9.31 and 13.14 min. Mass spectrum analysis identified 5-(hydroxymethyl)-2-furancarboxaldehyde with the molecular formula C6H6O3 and a molecular weight of 126 g·mol−1 as the major compound, and 4-propyl benzaldehyde with a formula of C10H12O and a molecular weight of 148 g mol−1 as the minor compound, both resulting from the biodegradation of TNT by T. viride. In conclusion, T. viride could be used in microbial-based bioremediation technologies as a biological agent to eradicate the toxicity of the TNT explosive. In addition, future molecular-based studies should be conducted to clearly identify the enzymes and the corresponding genes that give T. viride the ability to degrade and remediate TNT explosives. This could help in the eradication of soils contaminated with explosives or other toxic biohazards.

1H,4H-Piperazine-diium Dichlorosulfonate: Structure Elucidation and its Dual Solvent–Catalyst Activity for the Synthesis of New Dihydro-[1,2,4]triazolo[1,5-a]pyrimidine Scaffolds

A new ionic liquid containing a 1H,4H-piperazine-diium ring and chlorosulfonate as a 1,4-dicationic core and counter ion, respectively, was designed and synthesised. The structure elucidation of this ionic liquid was conducted by 1D and 2D NMR, FT-IR, Raman, and mass spectrum analysis. The physical properties of this ionic liquid were determined and reported. Furthermore, the dual solvent–catalyst activity of piperazine-1,4-diium dichlorosulfonate was investigated for the synthesis of new dihydro[1,2,4]triazolo[1,5-a]pyrimidines through a one-pot three-component reaction. The ionic liquid was retrieved and reused several times without reducing its catalytic efficiency.

Synthesis and Evaluation of Some 2–Aryl–3–[Substituted Pyridin–2–Yl]-Amino/Methylamino Thiazolidin-4-Ones

A series of compounds incorporating thiazolidinone moiety has been synthesized and screened for their antifungal activity. 2-Aryl-3-[substituted pyridin-2-yl]-amino/methylamino thiazolidin-4-ones have been synthesized by cyclocondensation of [substituted pyridin-2-yl]- araldehydehydrazone and N-Methyl [substituted pyridin-2-yl]-araldehydehydrazone with mercapto acetic acid in dioxane. The initial reactants required for the synthesis were obtained by refluxing 2-hydrazino substituted pyridine and 2-[N-methylhydrazino]-substituted pyridine with different substituted aldehydes. These newly synthesized compounds were then screened for their fungicidal activity against Rhizoctina solani and Fusarium oxysporum. Structures of all these compounds were confirmed by 1H NMR, IR and mass spectrum analysis. Some compounds exhibited excellent fungicidal properties.