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Colorectal cancer (CRC) is the third most common type of cancer as it accounts for approximately 7% of all cancer types. The goal of this study is to identify and analyze the differentially expressed genes (DEGs) in early-onset CRC (EOCRC) and late-onset CRC (LOCRC). The RNA-seq data was downloaded from GEO database and analyzed using GEO2R tool. This was followed by gene and pathway enrichment, detection of protein-protein interactions, predicting the governing transcriptional factors. Besides, survival rate and response to chemotherapy were also assessed. 250 DEGs were obtained, 235 down-regulated and 15 up-regulated. Extracellular structure organization, collagen-containing extracellular matrix, platelet-derived growth factor and protein digestion and absorption were the most common biological process, cellular compartment, molecular function and KEGG pathway. Moreover, ten hub genes were filtered, namely COL1A1, VWF, COL3A1, EGF, IGF1, COL1A2, ITGB3, COL11A2, COL6A1, CD163 as the top-ten hub genes while FOXC1, GATA2, YY1, TFAP2A and PPARG were predicted to be the most significant transcriptional factors controlling them. Only EGF was considered as prognostic biomarker while COL1A1 as predictive biomarker. In conclusion, the shortlisted hub genes account for the discrimination between EOCRC and LOCRC which should be further explored in-depth.

Background and Objectives: The present study was designed to assess the antileprotic effectiveness of some bioactive natural compounds towards enoyl acyl carrier protein reductase inhibition. Leprosy still constitutes a global pandemic in spite of long years of discovery. The current therapy option is multi-drug treatment using a combination of Dapsone, Rifampicin and Clofazimine. However, mycobacterium leprae counteracted by mutating the drug targets which necessitates the search for novel targets. One such target is enoyl acyl carrier protein reductase that mediates the fatty acid biosynthesis. Materials and Methods: Multiple (14) ligands of natural origin were drawn from PubChem database and their ADMET parameters were preicted using ADMETLab 2.0 webserver. After, the ligands were docked against the enzyme (PDB ID: 2NTV) at its active site using iGEMDOCK software. Results: ADMET parameters of the tested ligands proven to be accepted by Lipinski's rule of five except for two ligands. Furthermore, molecular docking results revealed that all of the tested compounds showed better binding energy than the reference drug Dapsone. The best of which was silymarin. Conclusion: The tested natural ligands have the capability to control M.leprae.

The aim of this study is to in silico screen new glucose-6-phosphate dehydrogenase (G6PD) inhibitors. glucose-6-phosphate dehydrogenase is the first and regulator of pentose phosphate pathway providing NADPH and ribose-5-phosphate required for various syntheses from fatty acids to DNA. G6PD is linked to oxidative stress and hence, to inflammation as well. Therefore, G6PD inhibition is a useful target against inflammation, cancer and some infections. Virtual screening of 15 ligands in the NADP-binding site in comparison with the standard inhibitor 6-aminonicotinamide using iGEMDOCK. Besides, ADME properties of the selected compounds were performed via SWISSADME webserver. All the tested ligands were better than reference inhibitor in terms of binding energy as well as pharmacokinetic and ADME parameters. Moreover, of all tested compounds, ligand 15 showed best docking fitness (-115 Kcal/mole total energy). Novel compounds were screened to be lead inhibitors of G6PD enzyme and ligand 15 ranked first.

Kinases catalyze phosphoryl transfer from a nucleoside triphosphate (usually ATP) to an amino acid residue on a protein (for activation purposes). These enzymes are well-appreciated drug targets against different viruses and cancers. However, some poxviruses are human and animal pathogens that lack effective therapeutic agents. In poxvirus, the production of infectious particles in the infected cells depends on F10 protein kinase that activates numerous proteins involved in the assembly of new virions. The ongoing outbreak of the human monkeypox virus (hMPXV) sparked the need for efficient antiviral drugs to control such outbreaks and lower their burden. In this work, we employed state-of-the-art computational resources to elucidate the structure of the major kinase in hMPXV using AlphaFold2. The predicted structure shows the atypical nature of this kinase; nonetheless, the overall structural fold is roughly conserved. Calculations of binding free energy determined the hotspot residues contributing to phosphate source (ATP) via Molecular Mechanics with Generalized Born and Surface Area solvation (MM/GBSA). The structural analysis in this work provides the basis for setting up a thorough experimental investigation to understand the enzymatic mechanism and development of small-molecule inhibitors against such a critical target.

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