Neoechinulin A as a Promising SARS-CoV-2 Mpro Inhibitor: In Vitro and In Silico Study Showing the Ability of Simulations in Discerning Active from Inactive Enzyme Inhibitors

The COVID-19 pandemic and its continuing emerging variants emphasize the need to discover appropriate treatment, where vaccines alone have failed to show complete protection against the new variants of the virus. Therefore, treatment of the infected cases is critical. This paper discusses the bio-guided isolation of three indole diketopiperazine alkaloids, neoechinulin A (1), echinulin (2), and eurocristatine (3), from the Red Sea-derived Aspergillus fumigatus MR2012. Neoechinulin A (1) exhibited a potent inhibitory effect against SARS-CoV-2 M^pro with IC₅₀ value of 0.47 μM, which is comparable to the reference standard GC376. Despite the structural similarity between the three compounds, only 1 showed a promising effect. The mechanism of inhibition is discussed in light of a series of extensive molecular docking, classical and steered molecular dynamics simulation experiments. This paper sheds light on indole diketopiperazine alkaloids as a potential structural motif against SARS-CoV-2 M^pro. Additionally, it highlights the potential of different molecular docking and molecular dynamics simulation approaches in the discrimination between active and inactive structurally related M^pro inhibitors.     

Perineal Nets of Proteoglycans and Glycoproteins in Albino Rat Hippocampus

Perineuronal nets (PNs) of condensed extracellular matrix (ECM) have been shown to characterize the microenvironment of individual neurons and the chemoarchitecture of some brain regions. In the present study, PNs in the hippocampus were visualized with a cationic iron colloid method for sulphated proteoglycan content and a plant lectin from Vicia villosa agglutinin (VVA) for N-acetylgalactosamine containing glycoconjugates. The ECM molecules were organized in reticular coats (PNs) around non-pyramidal cells in the Ammons horn (Corneu Ammons, CA) and subicular region, in addition to pyramidal neurons located in CA2 and CA3 regions. CA2 stratum pyramidale exhibited the most intense staining of its PNs and a diffuse intervening neutrophil labelling, while CA3 region showed a graded fashion of staining intensity. The subiculum displayed intensely stained perineuronal coats. Notably, the hippocampal perineuronal nets revealed overlapped staining characteristics with both staining methods. However, cell coats of the subicular neurons showed various degrees of labelling characteristics with both markers. It is suggested that the PNs in the hippocampus are correlated with the fast spiking inhibitory GABAergic neurons and their target pyramidal cells, and this is important to keep the excitatory elements under control and therefore control the information processes within the hippocampus.     

Preparation of controlled-release formulations of 14C-labelled thiobencarb herbicide and study of their environmental behaviour

Controlled-release formulations of ¹⁴C-labelled thiobencarb herbicide were prepared in calcium alginate using kaolin as an inexpensive filler. The rates of release of the herbicide from these and from a commercial granular formulation were studied in static distilled water contained in open and closed vessels. The rate of release of the herbicide was much higher from the commercial formulation than from the controlled-release formulations. Increasing the proportion of kaolin to calcium alginate in controlled-release formulations reduced the rate of release of the herbicide. There was a significant loss of thiobencarb-related radioactivity from the water solution when the vessels containing the solutions were left uncovered and exposed to light. The loss of the herbicide seemed to be due to degradation and evaporation.     

Ultrastructure of the thyroid gland of the one-humped camel (Camelus dromedarius)

Follicular epithelium of the thyroid gland of the one-humped camel was examined by light and electron microscopy. It consisted of a single type of epithelial cell which varied from flattened to columnar in shape. Follicular epithelial cells were characterized by the presence of markedly dilated cisternae of rough-surfaced endoplasmic reticulum, well developed Golgi apparatus, abundant small vesicles (150 nm to 200 nm in diameter) in the apical cytoplasm, and electron-dense colloid droplets measuring from 250 nm to 1600 nm. Follicular epithelial cells frequently showed apocrine secretion into colloidal lumens. Apocrine protrusions with smooth surface were dome-like or balloon-like structures and contained a fine granular matrix. These findings indicate that the morphological features of the follicular epithelial cells of the thyroid gland of the camel are essentially similar to those of mammals except for the presence of apocrine secretion, which is unique to the camel.     

Characterization of citrus germplasm including unknown variants by inter-simple sequence repeat (ISSR) markers

Inter-simple sequence repeat (ISSR) markers were used to study phylogenetic relationships among 33 citrus genotypes including several undefined local or native varieties as well as some known varieties in the Fars Province of Iran.     

Foliar Application of Glycinebetaine and Salicylic Acid Improves Growth,Yield and Water Productivity of Hybrid Sunflower Planted by Different Sowing Methods

Improved planting methods and foliar application of glycinebetaine (GB) and salicylic acid (SA) can improve the water productivity in field crops under limited water supply conditions. A 2‐year field study was conducted to evaluate the possible role of different planting methods and foliar applications of GB and SA in improving the yield, quality and water productivity of hybrid sunflower (Helianthus annuus L.). The crop was planted by flat sowing (75 cm spaced rows) and ridge sowing (75 cm spaced ridges), with GB and SA applied exogenously at 100 and 0.724 mm , respectively, at both budding and flowering stages, while control plots received distilled water. Ridge sowing, rather than flat sowing, improved the biological yield, oil yield, leaf area index (LAI), crop growth rate (CGR), plant height, water‐use efficiency and final achene yield during both the years. Foliar applications of GB and SA at both the stages improved the achene yield, although foliar application of GB at flowering was the most effective. Neither the planting methods nor the foliar application of GB and SA altered the achene oil contents during both the years. Foliar application of GB and SA increased the free proline content of the leaf and GB contents at flowering but reduced the achene protein contents, whereas planting method had no effect on these attributes across the years. Of the foliar applied chemicals, GB was more effective in improving sunflower growth and yield and water productivity than SA. To conclude, ridge sowing coupled with foliar application of GB at flowering stage could be beneficial for achieving maximum yields of hybrid sunflower under relatively water limited conditions in the field.     

Glycinebetaine Improves Chilling Tolerance in Hybrid Maize

Plant growth and development is hampered by various environmental stresses including chilling. We investigated the possibility of improving chilling tolerance in hybrid maize by glycinebetaine (GB) seed treatments. Maize hybrid (Hycorn 8288) seeds were soaked in 50, 100 and 150 mg l^?1 (p.p.m.) aerated solution of GB for 24 h and were dried back. Treated and untreated seeds were sown at 27 °C (optimal temperature) and at 15 °C (chilling stress) under controlled conditions. Germination and seedling growth was significantly hindered under chilling stress. Moreover, chilling stress significantly reduced the starch metabolism and relative water contents (RWC), and increased the membrane electrolyte leakage. However, activities of antioxidants (catalase, superoxide dismutase and ascorbate peroxidase) were increased under stress conditions. Seed treatments with GB improved the germination rate, root and shoot length, seedling fresh and dry weights, leaf and root scores, RWC, soluble sugars, α‐amylase activity and antioxidants significantly compared with untreated seeds under optimal and stress conditions. Induction of chilling tolerance was attributed to maintenance of high tissue water contents, reduced membrane electrolyte leakage, and higher antioxidant activities and carbohydrate metabolism. Seed treatment with 100 mg l^?1 GB was the best treatment for improving the performance of hybrid maize under normal and stress conditions compared with control and other levels used.