Aurasperone A Inhibits SARS CoV-2 In Vitro: An Integrated In Vitro and In Silico Study

Several natural products recovered from a marine-derived Aspergillus niger were tested for their inhibitory activity against SARS CoV-2 in vitro. Aurasperone A (3) was found to inhibit SARS CoV-2 efficiently (IC₅₀ = 12.25 µM) with comparable activity with the positive control remdesivir (IC₅₀ = 10.11 µM). Aurasperone A exerted minimal cytotoxicity on Vero E6 cells (CC₅₀ = 32.36 mM, SI = 2641.5) and it was found to be much safer than remdesivir (CC₅₀ = 415.22 µM, SI = 41.07). To putatively highlight its molecular target, aurasperone A was subjected to molecular docking against several key-viral protein targets followed by a series of molecular dynamics-based in silico experiments that suggested M^pro to be its primary viral protein target. More potent anti-SARS CoV-2 M^pro inhibitors can be developed according to our findings presented in the present investigation.     

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.     

Current status and prospects of farming the giant river prawn Macrobrachium rosenbergii (De Man) in Bangladesh

Giant river prawn (Macrobrachium rosenbergii) farming plays an important role in the economy of Bangladesh. Presently, it is cultured in around 50 000 ha area with total annual production of 23 240 t. Traditional extensive prawn farming has been expanding over the last three decades through the introduction and adoption of improved culture systems, such as culture of prawn‐carps, prawn‐shrimp‐fish and prawn‐fish‐rice as concurrent and rotational systems. Efforts for the development of improved techniques on broodstock management, seed production and rearing and grow‐out of prawn have been made over the last decade. The outcomes are low‐cost feed for broodstock, production of post‐larvae in net cages (hapa), all‐male prawn culture, periphyton based prawn‐tilapia culture, C/N based prawn culture, organic prawn farming, prawn‐mola culture and prawn‐carp‐mola polyculture. Despite the development of culture technologies, a number of challenges for sustainable development of prawn farming need to be overcome to realize the potentials of this promising sector. Good aquaculture practises at all levels and application of measures for quality control and food safety would ensure sustainable development of prawn farming in Bangladesh.     

Immunohistochemical demonstration of Leu-7 (HNK-1), Neurone-specific Enolase (NSE) and Protein-Gene Peptide (PGP) 9.5 in the developing camel (Camelus dromedarius) heart

The development of the heart-conducting system has been controversially discussed. The common opinion that these specialized myocytes originate from mesodermal precursors has been challenged when nerve-specific antigens (Leu-7, NF, GIN2) were demonstrated in embryonic hearts of various species, suggesting a neural crest contribution to the embryonic conducting tissue. Anti-Leu-7 (HNK-1) antibodies were reported to reliably mark the conducting system in developing rat, chicken and human hearts. The present investigation was carried out on the hearts of 15 camel fetuses at 35, 45, 60, 75 and 100 cm crown-rump length (three specimens for each stage), in addition to three adult hearts. We investigated the antigenicity of cardiac structures for Leu-7, NSE (Neurone specific Enolase) and PGP (Protein Gene Peptide) 9.5. In all specimens investigated, both NSE and PGP 9.5 were expressed by cardiac nerves and conducting system components. The sinuatrial and atrioventricular nodes, the atrioventricular bundle as well as subendocardial and intramyocardial Purkinje fibers were stained. In contrast, the developing conducting system did not react with anti-Leu-7 antibody, although Leu-7 antigenicity was strongly expressed by the developing cardiac nerves. In adult camel hearts, the same pattern of immunoreactivity for the markers studied was still retained. Our results show that the expression of marker proteins for the developing conducting system is species-specific. Therefore, these markers are of little significance in discussions on the possible neurogenic nature of the heart conducting tissue.     

Effect of Microsphaeropsis sp. Strain P130A on Germination and Production of Sclerotia of Rhizoctonia solani and Interaction Between the Antagonist and the Pathogen

Microsphaeropsis sp. strain P130A was evaluated for the control of tuber-borne inoculum of Rhizoctonia solani based on the viability of sclerotia produced in vitro and on both the viability and production of tuber-borne sclerotia. The interactions between the antagonist and the pathogen, as well as the effect of the toxins produced by the antagonist on mycelial growth of R. solani were studied using transmission electron microscopy. On sclerotia produced in vitro, for all incubation periods (1 to 42 days), Microsphaeropsis sp. significantly reduced germination. Percent germination of sclerotia treated with Microsphaeropsis sp. decreased with increasing incubation period from an average of 82.0% after 1 day to stabilize at an average of 5.8% after 35 days. Similarly, percent germination of tuber-borne sclerotia was significantly lower when tubers were treated with Microsphaeropsis sp. Both 2% formaldehyde and Microsphaeropsis sp. treatments significantly reduced sclerotia germination to approximately 10% after 42 days of incubation at 4 degrees C. Furthermore, on tubers treated with the antagonist, the number of sclerotia per square centimeter decreased from 1.6 to 0.5 during the 8 months of storage at 4 degrees C, whereas an increase from 1.2 to 7.8 sclerotia per square centimeter was observed on untreated tubers. Microsphaeropsis sp. (strain P130A) colonized hyphae of R. solani within 4 days after contact on culture media. Transmission electron microscopic observations showed that the antagonist induced a rupture of the pathogen plasma membrane and that a chitin-enriched matrix was deposited at sites of potential antagonist penetration. Host penetration was not associated with pathogen cell wall alterations, which occurred at the time of progress of the antagonist in the pathogen cytoplasm. In the presence of a crude extract of Microsphaeropsis sp., cells of R. solani showed cytoplasm disorganization and breakdown of plasma membranes. Antibiosis and mycoparasitism were involved in the antagonism of R. solani by Microsphaeropsis sp., but the sequence by which these events occur, as well as the significance of wall appositions produced by R. solani, is yet to be established.     

Renal adenocarcinoma, hepatocellular carcinoma, and pancreatic islet cell carcinoma in a binturong (Arctictis binturong).

A 19-yr-old binturong (Arctictis binturong) with acute upper respiratory disease was euthanized. Postmortem findings included hepatocellular carcinoma, pancreatic islet cell carcinoma, and renal adenocarcinoma with metastasis to the spleen, pleura, and pericardium. A link between primary hepatic and renal neoplasms has been noted in older humans.     

Insecticide resistance in cotton aphid Aphis gossypii (Glov.) in the Sudan Gezira

The resistance to insecticides of three Sudanese strains of A. gossypii (Glov.) collected from cotton fields in the Sudan Gezira Scheme over three seasons (1988, 1989, 1990) and that of two French strains was studied in the laboratory. When compared with a known susceptible strain, the aphids were found to be resistant-to the eight insecticides tested. Evolution of resistance in Sudanese strains during the three crop seasons was observed. Assay of aphid homogcnate for carboxytesterase activity towards the substrates α-naphthyl acetate and β-naphthyl acetate showed that there was no enhancement of this class of enzyme and thus it was not a cause of resistance in this species. A study of interaction between the acetylcholinesterase (AchE) and pirimicarb established the kinetics of the inhibition process. I₅₀ values were found to be much higher for the Sudanese strains than for the susceptible strain. First-order inhibition kinetics revealed that resistance towards pirimicarb in Sudanese-strains was caused by a modified AchE which had a reduced affinity (higher K_a value) and poor carbamylation ability (lower K₂ value) for pirimicarb. The resistance mechanisms for the other insecticides remain to be studied.     

Accumulation of phytoalexins in leaves of plane tree (Platanus spp.) expressing susceptibility or resistance toCeratocystis fimbriata f. sp.platani

Inoculation of leaves of resistantPlatanus occidentalis and susceptiblePlatanus acerifolia leaves withCeratocystis fimbriata f. sp.platani, the canker stain disease agent, induced foliar necrosis and biosynthesis of two phytoalexins, scopoletin and umbelliferone. Foliar symptoms keep localized and accumulation of coumarin phytoalexins was rapid for incompatible interactions. Necrosis spread widely and accumulation of these phenolic compounds was much later and lower for compatible interactions. The differential response could be used in a genetic improvement program for resistance against canker stain.     

Water Requirements of Safflower Entries in Middle Egypt

Two promising selected land races of safflower ( Carthamns tinctorious L.) designated as line 11 and line 13, together with the local variety Giza 1 , were examined under three levels of moisture depletions, i.e. 40, 60 and 80 % ASMD at Fayoum, Middle Egypt during 1986/87 and 1987/88 seasons. In both growing seasons, the second irrigation treatment i.e. 60 % ASMD gave the highest means for growth characters as well as seed yield and most of its components. Seed oil content per cent exhibited an increased as soil moisture depletion increased with no significant difference between entries. Safflower entries showed clear differences in some yield components which compensate each other and resulted in no significant difference in seed yield per hectar.
Consumptive use of water by safflower plants increased as the available soil moisture around the root zone increased. No significant differences were found in water consumed by safflower entries used in all experiments.
In the two experimental seasons, the best water use efficiency (WUE) for seed production was obtained also from the second treatment (60 % ASMD). The line 11 gave the best WUE.     

Relationship of toxoplasma infections to other diseases in dogs

Toxoplasma infection as detected by the immunofluorescent antibody (IFA) test was found in 13.2% of 448 dogs examined at the Purdue University Small Animal Clinic. Only titres of 1/64 and above were considered positive, but lesser titers were encountered more frequently. The highest titer observed was 1/1024 in 2 dogs one of which had idiopathic epilepsy and the other had dirofilariasis as well as hip dysplasia. The incidence of positive sera from male and female dogs were 11.7 and 14.5%, respectively. The highest frequency of infection occurred in young dogs up to 4 years of age and the lowest was in older animals. The presence of the high toxoplasmosis IFA titers in the sera of dogs seems to be associated with other disease conditions. Stress such as joint dislocations, fractures, helminth parasitism, and concomitant bacterial and viral infections, etc., was observed in 62.7% of the positive cases. Presence of tumors and renal disease conditions were associated with 28.8 and 5.2%, respectively, of the positive sera.