Density Functional Theory, Molecular Dynamics and AlteQ Studies Approaches of Baimantuoluoamide A and Baimantuoluoamide B to Identify Potential Inhibitors of Mpro Proteins: a Novel Target for the Treatment of SARS COVID-19.

COVID-19 has resulted in epidemi conditions over the world. Despite efforts by scientists from all over the world to develop an effective va ine against this virus, there is presently no recognized cure for COVID-19. The most succeed treatments for various ailments come from natural components found in medicinal plants, which are also rucial for the development of new medications. This study intends to understand the role of the baimantuoluoamide A and baimantuoluoamide B molecules in the treatment of Covid19. Initially, density functional theory (DFT) used to explore their electronic potentials along with the Becke3-Lee-Yang-Parr (B3LYP) 6-311 + G(d, p) basis set. A number of characteristics, including the energy gap, hardness, local softness, electronegativity, and electrophilicity, have also been calculated to discuss the reactivity of mole ules. Using natural bond orbital, the title compound's bioactive nature and stability were investigated. Further, both compounds potential inhibitors with main protease (Mpro) proteins, molecular dynamics simulations and AlteQ investigations also studied. Supplementary Information: The online version contains supplementary material available at 10.1134/S0021364023600039.

Experimental and Theoretical Studies of Green Synthesized Cu2O Nanoparticles Using Datura Metel L.

In biomedical applications, Cu2O nanoparticles are of great interest. The bioengineered route is eco-friendly for the synthesis of nanoparticles. Therefore, in the present study, there is an attempt to synthesis Cu2O nanoparticles using Datura metel L. The synthesized nanoparticles were characterized by UV-Vis, XRD, and FT-IR. UV-Vis results suggest the presence of hyoscyamine, atropine in Datura metel L, and also, nanoparticles formation has been confirmed by the presence of absorption peak at 790 nm. The average crystallite size (19.56 nm) was obtained by XRD. FT-IR was also used to confirm the different functional groups. Fourier Power Spectrum was also employed to examine the synthesized nanomaterials spectrum data to emphasize the peak of the prominent frequencies. Density functional theory (DFT) was also utilized to assess the energy of the substance over time, which appears to indicate a stable molecule. Furthermore, calculated energies, thermodynamic properties (such as enthalpies, entropies, and Gibbs-free energies), modeled structures of complexes, crystals, and clusters, and predicted yields, rates, and regio- and stereospecificity of reactions were all in good agreement with experimental results. Overall, the results show that the successful production of Cu2O nanoparticles with Datura metel L. corresponds to theoretical research.

[The comparative evalution of informativeness of immunologic and molecular genetic methods and means during stages of specific indication of melioidosis agent].

The reference-center of monitoring of agents of glanders and melioidosis carried out testing of reagents kits for diagnostic of agent of melioidosis and other close-related species of Burkholderiae in vitro. At the stage of specific identification of pathogenic Burkholderiae the diagnostic possibilities of commercial and experimental kits of reagents for express- and rapid analysis were evaluated. The criteria of evaluation of diagnostic value of kits of reagents were sensitivity, specificity and time of implementation of studies. The analysis with application of mono- and multi-locus amplification systems, including real-time polymerase chain reaction permitted during 5-6 hours to implement identification and differentiation of Burkholderia pseufomallei, B. thailandensis and B. cepacia.

Mutations in fd phage major coat protein modulate affinity of the displayed peptide.

Multibillion-clone libraries of phages displaying guest peptides fused to the major coat protein pVIII (landscape libraries) are a rich source of probes for proteinaceous and non-proteinaceous targets. As opposed to the pIII-type fusion phages, which display peptides as independent structural domains, the guest peptides in the pVIII-fusion phages can be structurally and functionally influenced by contiguous subunits. To decipher the impact of the locale of a guest peptide on its affinity characteristics, we constructed a library of phages carrying beta-galactosidase-binding peptide ADTFAKSMQ at the N-terminus of the pVIII protein surrounded by random amino acids. It was found that mutagenesis of amino acids 12-19 (domain C) has polar effects on target binding affinity of the displayed peptide. The phages with highest affinity are characterized by: (i) a net electrostatic charge around -1 of domain C of the mutated phages at pH 7.0; (ii) a lower radius of cylinder coaxial to alpha-helix formed by domain C; (iii) a lower higher occupied molecular orbital (HOMO) of domain C leading to a decreased formation of hydrogen bonds and (iv) positively charged surface and torsion energy of domain C, which may require a conformational transition of N-terminal peptide ADTFAKSMQ for its binding with beta-galactosidase. Influence of the guest peptide on the diversity of mutations in the neighboring landscape area was also observed.

[A study of conformational states of substrates of cytochrome P450 3A4].

A multiconformational study of substrates of cytochrome P450 3A4 has been carried out within the BiS/MC algorithm. The method allowed one to create a pseudoatomic model of the cytochrome and to find the substrate conformers responsible for the interaction with the cytochrome. It has been found that, in most cases, the geometry of the acting conformer is much different from the geometry of the global minimum conformer. It has been shown that the mirror conformational antipodes ("enantioconformers") are characterized as a rule by different Michaelis constants. A quantitative relationship between the Michaelis constants and the parameters of interactions in "model 3A4 isoform-substrate" complexes has been determined. The relationship describes the experimental value of Michaelis constant with the squared cross-validation correlation coefficient of 0.88.

[Identification of the agents of coccidioidomycosis using polymerase chain reaction].

Two pairs of primers for diagnosis of coccidioidomycosis using the method of PCR were constructed. One pair was used for identification of the two species of Coccidioides (C. immitis and C. posadasil) on the basis of MBP-1 gene. The other pair was chosen on the basis of SOWgp82 gene, which encodes an immunodominant, spherule outer wall glycoprotein for detecting only C. posadasii. The used primers allowed the agents of coccidioidomycosis to be detected using PCR with high sensitivity and specificity. The effective method of isolation of fungus DNA from soil contaminated with arthroconidia of Coccidioides spp. was developed. It includes guanidinthiocyanate-phenol-chloroform deproteinization followed by DNA purification using nuclear sorption.

[The modeling of interactions of the CYP2E1 isoform of human cytochrome P450 with substrates].

The interactions between the substrates of the 2E1 isoform of the human cytochrome P450 and receptor were simulated. It was found that the CP4 isoform of the cytochrome of the bacterial cell is highly homologous to the 2E1 isoform of the human cytochrome P450. The orientation of the substrates of the 2E1 isoform in the CP4 isoform of the bacterial cell cytochrome was performed. A cavity in the receptor was found that is responsible for the binding of the substrate. Amino acid residues Phe87, Pro89, Val119, Thr185, Leu244, Leu245, Leu246, Val247, Gly248, Gly249, Thr252, Val295, Asp297, Cys357, Ile395, and Val396, the heme, and water molecules are involved in the formation of the cavity. The mode of the interactions of the substrate molecule with cytochrome was analyzed. Active sites of the receptor, and a part of the substrate molecule responsible for the binding to cytochrome were found. Equations for the dependence of the Michaelis constant on the structural parameters of complexes of substrates with cytochrome were derived.

[Combined antibacterial and probiotic therapy of Helicobacter-associated diseases in children]. / Sochetannaia antibakterial'naia i probioticheskaia terapiia khelikobakterassotsiirovannykh zabolevanii u detei.

On the basis of microbiological monitoring and clinico-morphological criteria, the use of probiotics containing lacto- and bifidobacteria, simultaneously with "triple" antibacterial therapy (antibiotics of choice, metronidazole and bismuth salts), has been found to produce curative effect in the treatment of Helicobacter-associated gastroduodenal pathology in children. The influence of "triple" antibacterial therapy on the microecology of the gastrointestinal tract and the state of the immunobiological status of patients was studied. The combined scheme for correcting damaged microbiocenosis with probiotics in accordance with the concept of microecological adequacy is proposed. The scheme includes modern antibacterial therapy in combination with the probiotic preparations of lactobacteria. The prescription of bifidobacteria-containing probiotics is recommended at early stages from the beginning of etiotropic therapy. The effectiveness of the therapy may be dynamically evaluated, starting from week 5 after the end of the complex therapy, in EIA with the use of specific anti-Helicobacter antibodies.

[Frequency of detection of hepatitis B markers in various chronic diseases in children]. / Chastota vyiavleniia markerovvirusnogo gepatita B pri razlichnykh khronicheskikh zabolevaniiakh u detei.

Overall 995 children with different somatic chronic diseases were examined for viral hepatitis B markers demonstration using up-to-date highly sensitive methods (hemagglutination inhibition test, EIA). In the control group (children with acute intestinal infections), HBV-infection markers were discovered in 4.3%. Children with diabetes mellitus (13.1%), chronic renal diseases (18.9%), pulmonary diseases (32.8%), bronchial asthma (33.3%) and hemophilia (85.2%) are attributed to the group at greater risk for HBV infection. As a rule, the rate of HBV-infection markers demonstration in chronic somatic diseases was higher in considerable duration of the underlying illness. The overwhelming majority of the children examined had suffered subclinical forms of HBV-infection as shown by the disease history, whereupon they manifested antibodies against HBV antigens. HBs-antigenemia, that persisted for a long time (chronic HBV-infection) was demonstrable far less frequently. The authors provide evidence for the necessity of carrying out a broad-scale screening of HBV-infection markers in the indicated risk groups and vaccination against hepatitis B in children without HBsAG and without immunity to viral hepatitis B. The importance of measures aimed at preventing infections transmitted via blood is emphasized.

[Solubilization of cholesterol by sodium salts of bile and fatty acids]. / Soliubilizatsiia kholecterina natrievymn soliami zhelchnykh i xhirnykh kislot.

Solubilization of cholesterol by sodium salts of cholic, glycocholic, deoxycholic, lithocholic and oleic acids was studied. Dynamics of the solubilization process is described and a comparative characteristic of solubilizing ability of the substances under investigation is given. Cholesterole solubilization is studied as dependent on the concentration of the given substances. The possible mechanisms of solubilization is discussed.