Discovery of Novel Peptidomimetics as Irreversible CHIKV NsP2 Protease Inhibitors Using Quantum Mechanical‐Based Ligand Descriptors

Chikungunya virus (CHIKV) is a mosquito‐borne alphavirus. Recent outbreaks of CHIKV infections have been reported in Asia, Africa, and Europe. The symptoms of CHIKV infection include fever, headache, nausea, vomiting, myalgia, rash, and chronic persistent arthralgia. To date, no vaccines or selective antiviral drugs against this important emerging virus have been reported. In this study, the design, synthesis, and antiviral activity screening of new topographical peptidomimetics revealed three potential prototype agents 3a , 4b, and 5d showing 93–100% maximum inhibition of CHIKV replication in cell‐based assay having EC₉₀ of 8.76–9.57 μg/mL. Intensive molecular modeling studies including covalent docking, lowest unoccupied molecular orbital energies, and the atomic condensed Fukui functions calculations strongly suggested the covalent binding of peptidomimetics 3a , 4b, and 5d to CHIKV nsP2 protease leading to permanent enzyme inactivation via Michael adduct formation between α/β‐unsaturated ketone functionality in our designed peptidomimetics and active site catalytic cysteine1013. Furthermore, small molecular weight peptidomimetics 3a and 4b satisfied the Lipinski rule of five for drug‐likeness and showed promising intestinal absorption and aqueous solubility via computational admet studies making them promising hits for further optimization.     

Laser-Assisted High Speed Machining of 316 Stainless Steel: The Effect of Water-Soluble Sago Starch Based Cutting Fluid on Surface Roughness and Tool Wear

Laser-assisted high speed milling is a subtractive machining method that employs a laser to thermally soften a difficult-to-cut material’s surface in order to enhance machinability at a high material removal rate with improved surface finish and tool life. However, this machining with high speed leads to high friction between workpiece and tool, and can result in high temperatures, impairing the surface quality. Use of conventional cutting fluid may not effectively control the heat generation. Besides, vegetable-based cutting fluids are invariably a major source of food insecurity of edible oils which is traditionally used as a staple food in many countries. Thus, the primary objective of this study is to experimentally investigate the effects of water-soluble sago starch-based cutting fluid on surface roughness and tool’s flank wear using response surface methodology (RSM) while machining of 316 stainless steel. In order to observe the comparison, the experiments with same machining parameters are conducted with conventional cutting fluid. The prepared water-soluble sago starch based cutting fluid showed excellent cooling and lubricating performance. Therefore, in comparison to the machining using conventional cutting fluid, a decrease of 48.23% in surface roughness and 38.41% in flank wear were noted using presented approach. Furthermore, using the extreme learning machine (ELM), the obtained data is modeled to predict surface roughness and flank wear and showed good agreement between observations and predictions.     

Toxicity of fungicides to Pisum sativum: a study of oxidative damage,growth suppression,cellular death and morpho-anatomical changes

Considering the fungicidal threat to the sustainable agro-environment, the toxicological impacts of three fungicides, namely kitazin, hexaconazole and carbendazim, on the biological, chemical and morpho-anatomical changes of peas were assessed. Fungicide applications in general caused a slow but gradual reduction in growth, symbiosis and yields of peas, which, however, varied appreciably among species and concentrations of the three fungicides. Of the three fungicides, carbendazim had the most lethal effect, in which it delayed seed germination and also diminished the overall pea growth. Carbendazim at 3000 μg kg⁻¹ maximally reduced the germination, SVI, size of roots and shoots and total dry matter accumulation in roots, shoots and whole plants distinctly by 40%, 84%, 72%, 73%, 68%, 75% and 73% (p ≤ 0.05), respectively. Hexaconazole at 120 μg kg⁻¹ significantly (p ≤ 0.05) declined total chlorophyll, carotenoids, grain yields, grain protein, root P and shoot N by 19%, 28%, 46%, 69%, 48% and 51%, respectively, over the control. The synthesis of stress biomarkers and oxidative stress were increased with increasing dosage rates of fungicides. Proline content in roots, shoots, leaves and grains, MDA, electrolyte leakage and H₂O₂ of plants grown in soil treated with 288 μg kg⁻¹ kitazin were increased significantly (p ≤ 0.05) by 73%, 52%, 41%, 24%, 59%, 40% and 27%, respectively, relative to the control. Antioxidant defence enzymes were greater in pea foliage. The SEM and CLSM images revealed an obvious alteration in root tips, enhanced cellular damage and cell death when plants were raised under fungicide stress. Also, morpho-anatomical variations in fungicide-treated foliage were visible in the SEM images. Overall, the present study suggests that a careful and secure strategy should be adopted before fungicides are chosen for enhancing pulse production in different agro-climatic regions.

Considering the fungicidal threat to the sustainable agro-environment, the toxicological impacts of three fungicides, namely kitazin, hexaconazole and carbendazim, on the biological, chemical and morpho-anatomical changes of peas were assessed.     

l-Proline catalyzed one-pot synthesis of polysubstituted pyridine system incorporating benzothiazole moiety via sustainable sonochemical approach

The efficient, highly convenient synthesis of polysubstituted pyridine derivatives was established via the reaction of N-(benzothiazol-2-yl)-2-cyanoacetamides with an assortment of arylidene malononitriles and arylidene ethyl cyanoacetates in the presence of l-proline as an efficient organocatalyst for this type of ultrasonic-mediated Michael addition. The mechanistic pathway and factors affecting this reaction were also established. The main characteristics of this procedure are high yields, use of a cost-effective catalyst, and easy work-up and purification.

The l-proline catalyzed ultrasonic-mediated synthesis of polysubstituted pyridone derivatives through the reaction of N-(benzothiazol-2-yl)-2-cyanoacetamides with an assortment of arylidenes has demonstrated as an efficient protocol.     

Prevalence and impact of comorbidities on disease prognosis among patients with COVID-19 in Bangladesh: A nationwide study amid the second wave

BackgroundSocio-demographics and comorbidities are involved in determining the severity and fatality in patients with COVID-19 suggested by studies in various countries, but study in Bangladesh is insufficient.AimsWe designed the study to evaluate the association of sociodemographic and comorbidities with the prognosis of adverse health outcomes in patients with COVID-19 in Bangladesh.MethodsA multivariate retrospective cohort study was conducted on data from 966 RT-PCR positive patients from eight divisions during December 13, 2020, to February 13, 2021. Variables included sociodemographic, comorbidities, symptoms, Charlson comorbidity index (CCI) and access to health facilities. Major outcome was fatality. Secondary outcomes included hospitalization, duration of hospital stay, requirement of mechanical ventilation and severity.ResultsMale (65.8%, 636 of 966) was predominant and mean age was 39.8 ± 12.6 years. Fever (79%), dry cough (55%), and loss of test/smell (51%) were frequent and 74% patients had >3 symptoms. Fatality was recorded in 10.5% patients. Comorbidities were found in 44% patients. Hypertension (21.5%) diabetes (14.6%), and cardiovascular diseases (11.3%) were most prevalent. Age >60 years (OR: 4.83, 95% CI: 2.45–6.49), and CCI >3 (OR: 5.48, 95% CI: 3.95–7.24) were predictors of hospitalizations. CCI >4 (aOR: 3.41, 95% CI: 2.57–6.09) was predictor of severity. Age >60 years (aOR: 3.77, 95% CI: 1.07–6.34), >3 symptoms (aOR: 2.14, 95% CI: 0.97–4.91) and CCI >3 vs. CCI <3 (aOR: 5.23, 95% CI: 3.77–8.09) were independently associated with fatality.ConclusionsIncreased age, >3 symptoms, increasing comorbidities, higher CCI were associated with increased hospitalization, severity and fatality in patients with COVID-19.     

Recent Advances in Polymer Nanocomposites Based on Polyethylene and Polyvinylchloride for Power Cables

Polymer nanocomposites used in underground cables have been of great interest to researchers over the past 10 years. Their preparation and the dispersion of the nanoparticles through the polymer host matrix are the key factors leading to their enhanced dielectric properties. Their important dielectric properties are breakdown strength, permittivity, conductivity, dielectric loss, space charge accumulation, tracking, and erosion, and partial discharge. An overview of recent advances in polymer nanocomposites based on LDPE, HDPE, XLPE, and PVC is presented, focusing on their preparation and electrical properties.