Bioinformatics and systems biology analysis revealed PMID26394986-Compound-10 as potential repurposable drug against covid-19.

The global health pandemic known as COVID-19, which stems from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a significant concern worldwide. Several treatment methods exist for COVID-19; however, there is an urgent demand for previously established drugs and vaccines to effectively combat the disease. Since, discovering new drugs poses a significant challenge, making the repurposing of existing drugs can potentially reduce time and costs compared to developing entirely new drugs from scratch. The objective of this study is to identify hub genes and associated repurposed drugs targeting them. We analyzed differentially expressed genes (DEGs) by analyzing RNA-seq transcriptomic datasets and integrated with genes associated with COVID-19 present in different databases. We detected 173 Covid-19 associated genes for the construction of a protein-protein interaction (PPI) network which resulted in the identification of the top 10 hub genes/proteins (STAT1, IRF7, MX1, IRF9, ISG15, OAS3, OAS2, OAS1, IRF3, and IRF1). Hub genes were subjected to GO functional and KEGG pathway enrichment analyses, which indicated some key roles and signaling pathways that were strongly related to SARS-CoV-2 infections. We conducted drug repurposing analysis using CMap, TTD, and DrugBank databases with these 10 hub genes, leading to the identification of Piceatannol, CKD-712, and PMID26394986-Compound-10 as top-ranked candidate drugs. Finally, drug-gene interactions analysis through molecular docking and validated via molecular dynamic simulation for 80 ns suggests PMID26394986-Compound-10 as the only potential drug. Our research demonstrates how in silico analysis might produce repurposing candidates to help respond faster to new disease outbreaks.Communicated by Ramaswamy H. Sarma.

Comparative molecular docking analysis for analyzing the inhibitory effect of Anakinra and Ustekinumab against IL17F.

Interleukin 17 F is a member of IL-17 cytokine family with a 50% structural homology to IL-17A and plays a significant role either alone or in combination with IL-17A towards inflammation in Rheumatoid arthritis (RA). A growing number of drugs targeting IL-17 pathway are being tested against population specific disease markers. The major objective of this research was to investigate the anti-inflammatory effect of Anakinra (an IL-1 R1 inhibitor) and Ustekinumab (an IL-12 and IL-23 inhibitor) by targeting IL17F. The three dimensional structures of IL17F was taken from PDB while structures of drugs were taken from PubChem database. Docking was performed using MOE and Schrodinger ligand docking software and binding energies, including s-score using London-dG fitness function and glide score using glide internal energy function, between drug and targets were compared. Furthermore, Protein-Drug complex were subjected to 150 ns Molecular Dynamics (MD) Simulations using Schrodinger's Desmond Module. Docking and MD simulation results suggest anakinra as a more potent IL17F inhibitor and forming a more structurally stable complex.Communicated by Ramaswamy H. Sarma.

Ginger Loaded Polyethylene Oxide Electrospun Nanomembrane: Rheological and Antimicrobial Attributes.

Synthetic antibiotics have captured the market in recent years, but the side effects of these products are life-threatening. In recent times, researchers have focused their research on natural-based products such as natural herbal oils, which are eco-friendly, biocompatible, biodegradable, and antibacterial. In this study, polyethylene oxide (PEO) and aqueous ginger extract (GE) were electrospun to produce novel antibacterial nanomembrane sheets as a function of PEO and GE concentrations. A GE average particle size of 91.16 nm was achieved with an extensive filtration process, inferring their incorporation in the PEO nanofibres. The presence of the GE was confirmed by Fourier transform infrared spectroscopy (FTIR) through peaks of phenol and aromatic groups. The viscoelastic properties of PEO/GE solutions were analysed in terms of PEO and GE concentrations. Increasing PEO and GE concentrations increased the solution's viscosity. The dynamic viscosity of 3% was not changed with increasing shear rate, indicating Newtonian fluid behaviour. The dynamic viscosity of 4 and 5 wt% PEO/GE solutions containing 10% GE increased exponentially compared to 3 wt%. In addition, the shear thinning behaviour was observed over a frequency range of 0.05 to 100 rad/s. Scanning Electron Microscopy (SEM) analysis also specified an increase in the nanofibre's diameter with increasing PEO concentration, while SEM images displayed smooth morphology with beadless nanofibres at different PEO/GE concentrations. In addition, PEO/GE nanomembranes inhibited the growth of Staphylococcus aureus, as presented by qualitative antibacterial results. The extent of PEO/GE nanomembrane's antibacterial activity was further investigated by the agar dilution method, which inhibited the 98.79% Staphylococcus aureus population at 30% GE concentration.

Progress in research: Daratumumab improves treatment outcomes of patients with AL amyloidosis.

Outcomes for patients with systemic light-chain (AL) amyloidosis have improved over the last two decades with timely diagnosis, use of novel chemotherapeutic agents, risk stratification and better patient selection criteria before hematopoietic autologous stem cell transplant (ASCT). However, majority of patients have advanced stage disease at initial presentation and at relapse rendering them ineligible for intensive cytotoxic chemotherapy or ASCT. Daratumumab (Dara) with or without standard chemotherapy appears to be an excellent treatment option for newly diagnosed and relapsed refractory AL amyloidosis. This is largely due to its tolerable safety and remarkable efficacy as seen in multiple retrospective, small phase II studies as well as a phase III randomized controlled trial. Here we review published clinical trials and retrospective data of Dara in AL amyloidosis that explore its role as a valuable addition to the treatment armamentarium for this challenging disease.

Micro-morphological response of some native dicotyledonous species to particulate pollutants emitted from stone crushing activities.

Stone crushing processes release particulates and associated noxious substances in our surroundings that are continuously destructing environmental conditions and ecosystem health. Morpho-anatomical changes in some medicinally important native species (Aerva javanica, Calotropis procera, Digera muricata, Euphorbia prostrata, Euploca strigosa, and Peganum harmala) exposed to heavy dust pollution were evaluated. These species selected on the basis of their ubiquitous distribution in the area. Two sites were selected in the Kirana Hills, Sargodha, one near stone crushers within 500-m radius (polluted) and the other 4 km away from the crushers (control) varying significantly in amount of dust particles received. A decrease in plant height of all species from dust-polluted sites was observed. Reduction in height was more prominent in species like C. procera and D. muricata. Stem sclerification increased in C. procera and E. prostrata from the polluted site that is an indication of better tolerance to dust pollution. C. procera showed increased stem and leaf epidermis, stem sclerenchyma, and stem vascular bundles, which can increase resistance to dust pollution. E. strigosa was the most sensitive species in which all morpho-anatomical factors decreased. Survival of plant species depended on specific structural modifications in dermal, mechanical, parenchymatous, and vascular tissue. Overall, dust pollution severely affected plant morphological and micro-morphological traits, but the response of selected species to dust pollution was variable. It is concluded that stem and leaf anatomical traits like size of dermal and storage tissue thickness and stomatal density are good indicators for biomonitoring of dust pollution.