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.     

Adaption of a formula for simulating bedload transport in the Nile River,Egypt

Journal of Soils and Sediments - Bedload transport discharge is important in river engineering and morphodynamics. The Meyer-Peter and Müller (MPM) equation for determining bedload transport...     

Inhibin and reproduction. First communication: changes to inhibin level in Barki ewes after artificial infection with bluetongue virus

Bluetongue virus type 16, isolated from sheep in Egypt, was injected to 4 normally cycling Barki ewes and caused high levels of inhibin. This was assayed by a biological method, using suppression of the luteinising hormone (LH) of castrated rats. Albumin (fraction 2) was injected to normally cycling ewes. The sera of injected ewes were investigated 1 day after injection and weekly up to the 4th one injection. There was a gradual decrease of LH (4.8 +/- 0.52 I.U./ml serum) until the minimum level (1.17 +/- 0.25 I.U./ml serum) was reached, in comparison to the control serum LH which was 5.26 +/- 0.52 I.U./ml serum during the dioestrous phase.     

Ultrastructure of Camel (Camelus dromedarius) Spermatozoa

Spermatozoa collected from the caudae epididymidis of six camels were examined by phase contrast, scanning electron and transmission electron microscopy. A comparison of the morphology of the camel spermatozoa with that of other domestic animals is presented.     

Inbreeding depression for economically important traits of Mazandaran native fowls

1. The objective was to investigate inbreeding depression for some economic traits of Mazandaran native fowls using data collected from 1992 to 2012 (21 generations) using a REML animal model of significant fixed and random effects with inbreeding of birds and dams as covariates.

2. The mean inbreeding coefficient (F) for the whole population and dams was 4.67% and 4.12%, respectively, and most of the inbred birds (75.79%) and inbred dams (72.58%) had F < 12.5%.

3. Individual and dam inbreeding trends were 0.55% and 0.53% per year.

4. Inbreeding depression for body weight at hatch, at 8 weeks and 12 weeks of age, age at sexual maturity, weight at sexual maturity, egg weight at 1st d of laying and average egg weight at 28, 30 and 32 weeks of laying due to a 1% increase in individual inbreeding were ?0.11 g, ?3.1 g, ?1.3 g, 0.15 d, 0.59 g, ?0.05 g and ?0.03 g, respectively.

5. A 1% increase in maternal inbreeding resulted in a reduction of 0.06, 0.6 and 3.6 g in body weight at hatch, 8 weeks and 12 weeks of age.

     

Evaluation of embryonic age and the effects of different proteases on the isolation and primary culture of chicken intestinal epithelial cells in vitro

The present study evaluates the effects of embryonic age and proteolytic enzymes on the isolation and primary culture of chicken enterocyte and to establish an effective technique for chicken intestinal epithelial cell (IEC) cultivation. Fourteen‐day‐old, 16‐day‐old and 18‐day‐old embryos (average weight: 52.23 ± 0.76 g, 50.86 ± 0.99 g, 48.98 ± 1.03 g) were the source for preparation of enterocyte culture, and trypsin‐ethylene diamine tetraacetic acid, collagenase, thermolysin and combination of collagenase and thermolysin were used for digestion medium. Optimal culture protocols were determined by qualitative assays of proliferation. Cells isolated by using 14‐day‐old embryo and collagenase obtain the best attachment and growth in culture, and the production of continuously growing IEC cultures. Thus, we conclude that the use of collagenase as a dissociating enzyme and 14‐day‐old embryo as a source can be advantageously applied to the isolation of chicken IEC and this method may be useful for various applications and basic studies of the intestinal tract concerning such objects as physiology, immunology and toxicology.     

Effect of feeding time and frequency on the growth and feed utilization of African catfish Clarias gariepinus (Burchell 1822) fingerlings

The effects of feeding time and frequency on the growth, feed utilization and survival of Clarias gariepinus (Burchell 1822; family Clariidae) fingerlings were evaluated in a 25-day study. Groups of African catfish with an initial individual weight of 0.98 ± 0.02 g were offered feeds continuously for 24 h, or during the day or night at different time intervals, with varying meal size. The growth rate was significantly affected by meal times. Widely practised day time feeding with three equal size meals a day gave the lowest growth and highest food wastage. The growth rates of fish fed continuously or during night time following their feed demand were significantly higher with lowest food conversion ratios and food wastage.     

Comparison of genetic variation among accessions of <Emphasis Type="Italic">Aegilops tauschii</Emphasis> using AFLP and SSR markers

Genetic diversity of 54 accessions of Aegilops tauschii from five countries was assessed using sequence-tagged microsatellites (or simple sequence repeats, SSRs) and amplified fragment length polymorphisms (AFLPs). In the case of AFLP analysis, a total of 256 amplification products obtained, 234 of them were polymorphic across all the 54 accessions. A total of 224 fragments were obtained from the 24 SSR primers and 219 of fragments were polymorphic across all the genotypes screened. Based on both AFLP and SSR markers, the highest percentage of polymorphisms were obtained in Iranian and accessions of unknown origin. The highest polymorphic information content (PIC) value was observed for SSRs (0.82) while the highest marker index (MI) value was for AFLPs (8.5) reflecting the hyper-variability of the first and the distinctive nature of the second system. Principal co-ordinate analysis (PCO) revealed congruent patterns of genetic relationships for both data sets, but did not group accessions strictly according to their geographical origins. Poor correlation was found between AFLP and SSR marker loci. This low association may be due to low number of AFLP and SSR markers. These results show that molecular markers can help to organize the genetic variability and expose useful diversity for breeding purposes.