Ligand and Structure-Based In Silico Determination of the Most Promising SARS-CoV-2 nsp16-nsp10 2′-o-Methyltransferase Complex Inhibitors among 3009 FDA Approved Drugs

As a continuation of our earlier work against SARS-CoV-2, seven FDA-approved drugs were designated as the best SARS-CoV-2 nsp16-nsp10 2′-o-methyltransferase (2′OMTase) inhibitors through 3009 compounds. The in silico inhibitory potential of the examined compounds against SARS-CoV-2 nsp16-nsp10 2′-o-methyltransferase (PDB ID: (6W4H) was conducted through a multi-step screening approach. At the beginning, molecular fingerprints experiment with SAM (S-Adenosylmethionine), the co-crystallized ligand of the targeted enzyme, unveiled the resemblance of 147 drugs. Then, a structural similarity experiment recommended 26 compounds. Therefore, the 26 compounds were docked against 2′OMTase to reveal the potential inhibitory effect of seven promising compounds (Protirelin, (1187), Calcium folinate (1913), Raltegravir (1995), Regadenoson (2176), Ertapenem (2396), Methylergometrine (2532), and Thiamine pyrophosphate hydrochloride (2612)). Out of the docked ligands, Ertapenem (2396) showed an ideal binding mode like that of the co-crystallized ligand (SAM). It occupied all sub-pockets of the active site and bound the crucial amino acids. Accordingly, some MD simulation experiments (RMSD, RMSF, R_g, SASA, and H-bonding) have been conducted for the 2′OMTase—Ertapenem complex over 100 ns. The performed MD experiments verified the correct binding mode of Ertapenem against 2′OMTase exhibiting low energy and optimal dynamics. Finally, MM-PBSA studies indicated that Ertapenem bonded advantageously to the targeted protein with a free energy value of −43 KJ/mol. Furthermore, the binding free energy analysis revealed the essential amino acids of 2′OMTase that served positively to the binding. The achieved results bring hope to find a treatment for COVID-19 via in vitro and in vivo studies for the pointed compounds.     

Immunomodulatory Efficacy-Mediated Anti-HCV and Anti-HBV Potential of Kefir Grains; Unveiling the In Vitro Antibacterial,Antifungal, and Wound Healing Activities

The utilization of fermented foods with health-promoting properties is becoming more popular around the world. Consequently, kefir, a fermented milk beverage made from kefir grains, was shown in numerous studies to be a probiotic product providing significant health benefits. Herein, we assessed the antibacterial and antifungal potential of kefir against a variety of pathogenic bacteria and fungi. This study also showed the effectiveness of kefir in healing wounds in human gastric epithelial cells (GES-1) by (80.78%) compared with control (55.75%) within 48 h. The quantitative polymerase chain reaction (qPCR) results of kefir-treated HCV- or HBV- infected cells found that 200 µg/mL of kefir can eliminate 92.36% of HCV and 75.71% of HBV relative to the untreated infected cells, whereas 800 µg/mL (the highest concentration) completely eradicated HCV and HBV. Moreover, the estimated IC₅₀ values of kefir, at which HCV and HBV were eradicated by 50%, were 63.84 ± 5.81 µg/mL and 224.02 ± 14.36 µg/mL, correspondingly. Kefir can significantly suppress the elevation of TNF-α and upregulate IL-10 and INF-γ in both treated HCV- and HBV-infected cells. High-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analysis of kefir revealed the presence of numerous active metabolites which mainly contribute to the antimicrobial, antiviral, and immunomodulatory activities. This study demonstrated, for the first time, the anti-HBV efficacy of kefir while also illustrating the immunomodulatory impact in the treated HBV-infected cells. Accordingly, kefir represents a potent antiviral agent against both viral hepatitis C and B, as well as having antimicrobial and wound healing potential.     

The Isolation and Characterization of Antagonist Trichoderma spp. from the Soil of Abha,Saudi Arabia

Background: The genus Trichoderma is widely spread in the environment, mainly in soils. Trichoderma are filamentous fungi and are used in a wide range of fields to manage plant patho-genic fungi. They have proven to be effective biocontrol agents due to their high reproducibility, adaptability, efficient nutrient mobilization, ability to colonize the rhizosphere, significant inhibitory effects against phytopathogenic fungi, and efficacy in promoting plant growth. In the present study, the antagonist Trichoderma isolates were characterized from the soil of Abha region, Saudi Arabia. Methodology: Soil samples were collected from six locations of Abha, Saudi Arabia to isolate Trichoderma having the antagonistic potential against plant pathogenic fungi. The soil dilution plate method was used to isolate Trichoderma (Trichoderma Specific Medium (TSM)). Isolated Trichoderma were evaluated for their antagonistic potential against Fusarium oxysporum, Alternaria alternata and Helminthosporium rostratum. The antagonist activity was assessed by dual culture assay, and the effect of volatile metabolites and culture filtrate of Trichoderma. In addition, the effect of different temperature and salt concentrations on the growth of Trichoderma isolates were also evaluated. Results: The most potent Trichoderma species were identified by using ITS4 and ITS 5 primers. Total 48 Trichoderma isolates were isolated on (TSM) from the soil samples out of those six isolates were found to have antagonist potential against the tested plant pathogenic fungi. In general, Trichoderma strains A (1) 2.1 T, A (3) 3.1 T and A (6) 2.2 T were found to be highly effective in reducing the growth of tested plant pathogenic fungi. Trichoderma A (1) 2.1 T was highly effective against F. oxysporum (82%), whereas Trichoderma A (6) 2.2 T prevented the maximal growth of H. rostratum (77%) according to the dual culture data. Furthermore, Trichoderma A (1) 2.1 T volatile metabolites hindered F. oxysporum growth. The volatile metabolite of Trichoderma A (6) 2.2 T, on the other hand, had the strongest activity against A. alternata (45%). The Trichoderma A (1) 2.1 T culture filtrate was proven to be effective in suppressing the growth of H. rostratum (47%). The temperature range of 26 °C to 30 °C was observed to be optimum for Trichoderma growth. Trichoderma isolates grew well at salt concentrations (NaCl) of 2%, and with the increasing salt concentration the growth of isolates decreased. The molecular analysis of potent fungi by ITS4 and ITS5 primers confirmed that the Trichoderma isolates A (1) 2.1 T, A (3) 3.1 and A (6) 2.2 T were T. harzianum, T. brevicompactum, and T. velutinum, respectively. Conclusions: The study concludes that the soil of the Abha region contains a large population of diverse fungi including Trichoderma, which can be explored further to be used as biocontrol agents.     

Enhanced FPGA realization of the fractional-order derivative and application to a variable-order chaotic system

Nonlinear Dynamics - The efficiency of the hardware implementations of fractional-order systems heavily relies on the efficiency of realizing the fractional-order derivative operator. In this work,...     

Statistical correlation of gain and buildup time in APDs and its effects on receiver performance

This paper reports a novel recurrence theory that enables us to calculate the exact joint probability density function (pdf) of the random gain and the random avalanche buildup time in avalanche photodiodes (APDs) including the effect of dead space. Such calculations reveal a strong statistical correlation between the gain and the buildup time for all widths of the multiplication region. To facilitate the calculation of the photocurrent statistics in the presence of this correlation, the impulse-response function of the APD is approximately modeled by a function of time whose prespecified shape is appropriately parameterized by two random variables: the gain and the buildup time. The evaluation of the variance of the photocurrent under this model leads to the definition of the shot-noise-equivalent bandwidth of the APD, which captures the statistical correlation between the gain and the buildup time. It is shown that the shot-noise-equivalent bandwidth in GaAs APDs is greater, by approximately 30%, than the traditional buildup-time-limited 3-dB bandwidth, which is calculated from the mean of the impulse-response function. A thorough analysis of the performance of APD-based integrate-and-dump digital receivers reveals that the strong correlation between the gain and the buildup time accentuates intersymbol interference (ISI) noise, and thus, adversely affects receiver sensitivity at high transmission rates beyond previously known limits.     

The Moore–Penrose Pseudoinverse: A Tutorial Review of the Theory

In the last decades, the Moore–Penrose pseudoinverse has found a wide range of applications in many areas of science and became a useful tool for physicists dealing, for instance, with optimization problems, with data analysis, with the solution of linear integral equations, etc. The existence of such applications alone should attract the interest of students and researchers in the Moore–Penrose pseudoinverse and in related subjects, such as the singular value decomposition theorem for matrices. In this note, we present a tutorial review of the theory of the Moore–Penrose pseudoinverse. We present the first definitions and some motivations, and after obtaining some basic results, we center our discussion on the spectral theorem and present an algorithmically simple expression for the computation of the Moore–Penrose pseudoinverse of a given matrix. We do not claim originality of the results. We rather intend to present a complete and self-contained tutorial review, useful for those more devoted to applications, for those more theoretically oriented, and for those who already have some working knowledge of the subject.