Computational screening approaches for investigating potential activity of phytoligands against SARS-CoV-2

Objective: SARS-CoV-2 causes COVID-19, a life-threatening respiratory illness with high rates of morbidity and mortality. As on date, there is no specific medicine to prevent or treat COVID-19. Therefore, there is an acute need to identify evidence-based holistic and safe mitigators.Methods: The present study is aimed to screen ligands of herbal origin using rationale based bioprospection analysis and subsequently predict their binding potential subdue the major drug targets for novel Coronavirus by employing computer-aided virtual screening. Further, comparative analysis of the binding potential of an approved chemical analogue and selected herbal ligands were also predicted. The selection of receptors was performed based on their pathophysiological relevance, as assessed by a PubMed based keyword hits matrix analysis. The drug likeliness and ADMETox descriptors of 24 herbal ligands were computationally predicted. Docking studies were further conducted with those phytoligands that qualified these parameters. An existing antimalarial drug, hydroxychloroquine, was also docked with all the selected viral receptors and its theoretical binding energy was set up as a standard for comparison as well as scrutinization of binding energies of the phytoligands. Results: The docking studies suggested that the herbal ligand, namely, gamma-glutamyl-S-allylcysteine demonstrated highly significant binding energies with viral spike glycoprotein, endoribonuclease and main protease (binding energy ≥ -490 kcal/mol for all the tested viral receptors).Conclusion: Gamma-glutamyl-S-allylcysteine demonstrated more significant binding potential as compared to the known chemical analogue, i.e., hydroxychloroquine, as observed in the computational docking studies. This study serves to present pre-eminent information for further clinical studies highlighting the utility of herbal ligands as probable lead molecules for mitigating novel Coronavirus infection.

Vinblastine and vincristine as anticancer molecules stopping the tubulin dimers

Vinblastine is belonging to vinca alkaloid family which is a chemical analogue of vincristine molecules. It has a high potential for attaching to tubulin of microtubules, therefore inhibiting the assembly of that biomolecules. Human EGFRs receptors are cell surfaces receptors proteins including three different domains which are known extracellular ligand-binding domain, trans-membranes hydrophobic domain and cytoplasmic C-terminal domain with tyrosine kinase. The Chemical & physical vibrational spectral data obtained from NMR, NBO and IR spectra based on the results of the theoretical calculations using DFT and HF methods. The fundamental vibrational modes were characterized depending on the stabilities of Herceptin in different dielectric constants. Thus, the goal of this article is to evaluate and quantify and qualify of the mechanism in various solvents.

Structural insights into the catalytic mechanism of Bacillus subtilis BacF

The nonribosomal biosynthesis of the dipeptide antibiotic bacilysin is achieved by the concerted action of multiple enzymes in the Bacillus subtilis bac operon. BacF (YwfG), encoded by the bacF gene, is a fold type I pyridoxal 5-phosphate (PLP)-dependent stereospecific transaminase. Activity assays with L-phenylalanine and 4-hydroxyphenylpyruvic acid (4HPP), a chemical analogue of tetrahydrohydroxyphenylpyruvic acid (H4HPP), revealed stereospecific substrate preferences, a finding that was consistent with previous reports on the role of this enzyme in bacilysin synthesis. The crystal structure of this dimeric enzyme was determined in its apo form as well as in substrate-bound and product-bound conformations. Two ligand-bound structures were determined by soaking BacF crystals with substrates (L-phenylalanine and 4-hydroxyphenylpyruvate). These structures reveal multiple catalytic steps: the internal aldimine with PLP and two external aldimine conformations that show the rearrangement of the external aldimine to generate product (L-tyrosine). Together, these structural snapshots provide an insight into the catalytic mechanism of this transaminase.

NAADP and the two-pore channel protein 1 participate in the acrosome reaction in mammalian spermatozoa

The functional relationship between the formation of hundreds of fusion pores during the acrosome reaction in spermatozoa and the mobilization of calcium from the acrosome has been determined only partially. Hence, the second messenger NAADP, promoting efflux of calcium from lysosome-like compartments and one of its potential molecular targets, the two-pore channel 1 (TPC1), were analyzed for its involvement in triggering the acrosome reaction using a TPCN1 gene–deficient mouse strain. The present study documents that TPC1 and NAADP-binding sites showed a colocalization at the acrosomal region and that treatment of spermatozoa with NAADP resulted in a loss of the acrosomal vesicle that showed typical properties described for TPCs: Registered responses were not detectable for its chemical analogue NADP and were blocked by the NAADP antagonist trans-Ned-19. In addition, two narrow bell-shaped dose-response curves were identified with maxima in either the nanomolar or low micromolar NAADP concentration range, where TPC1 was found to be responsible for activating the low affinity pathway. Our finding that two convergent NAADP-dependent pathways are operative in driving acrosomal exocytosis supports the concept that both NAADP-gated cascades match local NAADP concentrations with the efflux of acrosomal calcium, thereby ensuring complete fusion of the large acrosomal vesicle.

Influence of soil humic acid and fulvic acid on sorption of thorium(IV) on MX-80 bentonite

SummaryTh(IV) is considered herein as a chemical analogue of other actinides (IV). Effect of pH, ionic strength and humic acid/fulvic acid concentrations on the sorption of thorium(IV) to MX-80 bentonite was studied by batch technique. The sorption isotherms were acquired by varying pH in the range of 0.5–12 and FA/HA concentration in the range of 2–20 mg/L. The results indicate that soil fulvic acid has higher carboxylic content than humic acid, and has stronger positive influence on the sorption of Th(IV) on bentonite at low pH values than humic acid. The increase of FA/HA concentration results in a slight increase of Th(IV) sorption on FA/HA coated bentonite. The results of no drastic effect of different addition sequences of FA/HA and Th(IV) to bentonite suspension on Th(IV) sorption in the ternary system HA/FA-Th(IV)-bentonite indicate that both the Th(IV)-HA/FA complexation and HA/FA-bentonite sorption do not affect the sorption of Th(IV) on HA/FA coated bentonite obviously. The samples were also measured by SEM method and the results show that the surface properties of different samples are different.

Rhenium migration at the Maqarin natural analogue site (Jordan)

Rock analysis and study of groundwater data was combined with a short duration column experiment in order to better understand the behavior of rhenium (Re) in the site of Maqarin (Jordan). Results show that the combustion metamorphism having affected rock masses in Maqarin (Jordan), and led to the formation of “natural cements”, has strongly modified the spatial distribution of several elements, among which Re, creating a specific source term for this element leached by groundwaters. Unaltered cements are shown to contain up to 1.2 μg/g Re to be compared to 0.15 μg/g in the initial biomicrite. Re is rapidly leached from unaltered cements and can be used as a tracer of recent cement alteration episodes. Preliminary data suggest that Re, a chemical analogue of Tc, could be partially retained in fracture minerals.