Targeting CoV-2 spike RBD and ACE-2 interaction with flavonoids of Anatolian propolis by in silico and in vitro studies in terms of possible COVID-19 therapeutics

Propolis is a multi-functional bee product rich in polyphenols. In this study, the inhibitory effect of Anatolian propolis against SARS-coronavirus-2 (SARS-CoV-2) was investigated in vitro and in silico. Raw and commercial propolis samples were used, and both samples were found to be rich in caffeic acid, p-coumaric acid, ferulic acid, t-cinnamic acid, hesperetin, chrysin, pinocembrin, and caffeic acid phenethyl ester (CAPE) at HPLC-UV analysis. Ethanolic propolis extracts (EPE) were used in the ELISA screening test against the spike S1 protein (SARS-CoV-2): ACE-2 interaction for in vitro study. The binding energy values of these polyphenols to the SARS-CoV-2 spike and ACE-2 protein were calculated separately with a molecular docking study using the AutoDock 4.2.6 program. In addition, the pharmacokinetics and drug-likeness properties of these eight polyphenols were calculated according to the SwissADME tool. The binding energy value of pinocembrin was highest in both receptors, followed by chrysin, CAPE, and hesperetin. Based on the in silico modeling and ADME (absorption, distribution, metabolism, and excretion) behaviors of the eight polyphenols, the compounds exhibited the potential ability to act effectively as novel drugs. The findings of both studies showed that propolis has a high inhibitory potential against the Covid-19 virus. However, further studies are now needed.     

The Effects of Dietary Selenium and Vitamin E and their Combination on the Fatty Acids of Erythrocytes,Bone Marrow and Spleen Tissue Lipids of Lambs

The object was to determine the influence of dietary vitamin E, selenium and their combination on the fatty acid con-tent of erythrocytes, bone marrow and spleen lipids of Akkaraman lambs. After supplementation for 15 days, the amount of all fatty acids was slightly higher (p < 0·05) in the vitamin E as compared to the control group, whereas the amount of longer fatty acids was significantly higher (p < 0·01, p < 0·001) in the selenium and combination groups. On the thirtieth day, the amount of all fatty acids was slightly high (p < 0·5) in all the supplemented groups in comparison with the control group. In the bone marrow lipids, the amount of longer fatty acids was decreased (p < 0·05, p < 0·01, p < 0·001) in the vitamin E and combination groups as compared to the control. Although the amount of some fatty acids was high (p < 0·05, p < 0·01) in the selenium group compared to the control, linoleic (18:2), linolenic (18:3) and the polyunsaturated fatty acids (PUFA) were lower (p < 0·05, p < 0·001). In the spleen lipids, the amount of longer fatty acids was slightly decreased (p < 0·05) in the vitamin E group as compared with the control; however the amount of longer fatty acids was significantly higher (p < 0·05, p < 0·01) in the selenium and combination groups in comparison to the control group. Thus dietary supplementation with selenium was more effective than dietary vitamin E supplementation in altering the fatty acid content of the erythrocyte, bone marrow and spleen lipids. © 1997 John Wiley & Sons, Ltd.     

Analysis of heterotropic cooperativity in cytochrome P450 3A4 using alpha-naphthoflavone and testosterone

Cytochrome P450 3A4 (CYP3A4) displays non-Michaelis-Menten kinetics for many of the substrates it metabolizes, including testosterone (TST) and α-naphthoflavone (ANF). Heterotropic effects between these two substrates can further complicate the metabolic profile of the enzyme. In this work, monomeric CYP3A4 solubilized in Nanodiscs has been studied for its ability to interact with varying molar ratios of ANF and TST. Comparison of the observed heme spin state, NADPH consumption, and product formation rates with a non-cooperative model calculated from a linear combination of the global analysis of each substrate reveals a detailed landscape of the heterotropic interactions and indicates negligible binding cooperativity between ANF and TST. The observed effect of ANF on the kinetics of TST metabolism is due to the additive action of the second substrate with no specific allosteric effects.     

Mathematical modeling of gas-dynamic and radiative processes in experiments with the use of laser and heavy-ion beams

Results are presented from theoretical and experimental studies of gas-dynamic and radiative processes in the plasma that is planned to be used in future experiments on the stopping of fast heavy-ion beams. These experiments are aimed at measuring the enhanced (as compared to cold substance) plasma stopping power. To reliably interpret the experimental results, it is necessary to create a hydrodynamically stable homogeneous plasma with a uniform temperature and a lifetime exceeding the transit time of the heavy-ion beam (3–5 ns). The method for calculating plasma gas-dynamic characteristics with allowance for radiative heat transfer is described. The specific features of the so-called ion model of plasma, which is used to calculate plasma radiative characteristics, are discussed. The emission spectrum formed as a result of conversion of laser radiation into X-rays and the subsequent passing through a triacetate cellulose (C₁₂H₁₆O₈) target is calculated. The simulated spectrum of transmitted radiation satisfactorily agrees with experimental data.     

Rare case of manifestation of a proatlas

A two-sided lateral manifestation of the proatlas is described on the human macerated skull with formation of the atlas-proatlas articulations.     

Dimethyl sulfoxide binding to globular proteins: a nuclear magnetic relaxation dispersion study.

The 2H magnetic relaxation dispersion (NMRD) technique was used to characterize interactions of dimethyl sulfoxide (DMSO) with globular proteins. A difference NMRD experiment involving the N-acetylglucosamine trisaccharide inhibitor, demonstrated that the DMSO 2H NMRD profile in lysozyme solution is due to a single DMSO molecule bound in the active cleft, with a molecular order parameter of 0.47 +/- 0.05 and a residence time in the range 10 ns to 5 ms. With the aid of transverse 2H relaxation data, the upper bound of the residence time was further reduced to 100 microns. A 1H shift titration experiment was also performed, yielding a binding constant of 2.3 +/- 0.3 M-1 at 27 degrees C. In contrast to lysozyme, no DMSO dispersion was observed for bovine pancreatic trypsin inhibitor (BPTI), indicating that a stable DMSO-protein complex requires a cleft of appropriate geometry in addition to hydrogen-bond and hydrophobic interactions.     

Recombinant human alfa2-interferon (reaferon) in ointment form in the treatment of various diseases of the skin and mucosa

Clinical trials of the gene engineered human alpha 2-interferon as ointment were performed. The ointment was used in the treatment of patients with relapsing herpes of various localization, relapsing aphthous stomatitis and pemphigus vulgaris. It was shown that the ointment was harmless and its therapeutic effect was favourable. The preparation is recommended for introduction into the practice of public health.     

Experience with the methodological guidance of the on-the-job training of epidemiology graduates

Seven-year experience in the methodological guidance of the post-graduate specialization of medical graduates specializing in epidemiology has made it possible for the authors to come to the conclusion on the positive role of the on-the-job training of young specialists for a year after graduation, which is manifested by a shorter time necessary for their professional formation, the development of their capacity for making scientifically grounded, active solutions of practical problems. At the same time some defects, difficulties, and unsolved problems of on-the-job training have been revealed. The authors propose to organize internship also for this category of medical specialists and to carry out the specialization of all sanitary inspectors on the basis of "clinical" sanitary and epidemiological stations.