Discovery of Isojacareubin as a covalent inhibitor of SARS-CoV-2 main protease using structural and experimental approaches.

The ongoing pandemic with the emergence of immune evasion potential and, particularly, the current omicron subvariants intensified the situation further. Although vaccines are available, the immune evasion capabilities of the recent variants demand further efficient therapeutic choices to control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Hence, considering the necessity of the small molecule inhibitor, we target the main protease (3CLpro), which is an appealing target for the development of antiviral drugs against SARS-CoV-2. High-throughput molecular in silico screening of South African natural compounds database reported Isojacareubin and Glabranin as the potential inhibitors for the main protease. The calculated docking scores were reported to be -8.47 and -8.03 kcal/mol, respectively. Moreover, the structural dynamic assessment reported that Isojacareubin in complex with 3CLpro exhibit a more stable dynamic behavior than Glabranin. Inhibition assay indicated that Isojacareubin could inhibit SARS-CoV-2 3CLpro in a time- and dose-dependent manner, with half maximal inhibitory concentration values of 16.00 ± 1.35 µM (60 min incubation). Next, the covalent binding sites of Isojacareubin on SARS-CoV-2 3CLpro was identified by biomass spectrometry, which reported that Isojacareubin can covalently bind to thiols or Cysteine through Michael addition. To evaluate the inactivation potency of Isojacareubin, the inactivation kinetics was further investigated. The inactivation kinetic curves were plotted according to various concentrations with gradient-ascending incubation times. The KI value of Isojacareubin was determined as 30.71 µM, whereas the Kinact value was calculated as 0.054 min-1 . These results suggest that Isojacareubin is a covalent inhibitor of SARS-CoV-2 3CLpro .

Stability indicating RP-HPLC method of dexibuprofen in nanocream formulation: Identification and quantification.

A stability indicating reverse phase-HPLC method was designed for determination of dexibuprofen in drug solution and in nanocream formulation. Chromatographic conditions were optimized simply by adjusting the content and different compositions of reverse phase associated with mobile phases. Different parameters like specificity, limit of quantification (LOQ), limit of detection, linearity, range, system suitability, precision and accuracy were determined. Stability studies of dexibuprofen in nanocream were taken under the stressed situations of alkali, acid, oxidation process, UV and heat degradation. Tailing factor and % RSD were found >2000 and <2% respectively. The method was identified linear over the range of 0.2-1.6mg/ml having co-efficient of correlation 0.9995. Intra-day and inter- day precision and accuracy values for dexibuprofen were < 0.6% and <1.1032 and < 0.3% and 1.10% respectively. Stability studies showed that dexibuprofen was stable in nanocream against alkali, acid, oxidation, UV light and heat. The developed validated method was precise and accurate for the evaluation of dexibuprofen in solution as well as in nanocream formulation.

Abrogation of ORF8-IRF3 binding interface with Carbon nanotube derivatives to rescue the host immune system against SARS-CoV-2 by using molecular screening and simulation approaches.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to over six million deaths worldwide. In human immune system, the type 1 interferon (IFN) pathway plays a crucial role in fighting viral infections. However, the ORF8 protein of the virus evade the immune system by interacting with IRF3, hindering its nuclear translocation and consequently downregulate the type I IFN signaling pathway. To block the binding of ORF8-IRF3 and inhibit viral pathogenesis a quick discovery of an inhibitor molecule is needed. Therefore, in the present study, the interface between the ORF8 and IRF3 was targeted on a high-affinity carbon nanotube by using computational tools. After analysis of 62 carbon nanotubes by multiple docking with the induced fit model, the top five compounds with high docking scores of - 7.94 kcal/mol, - 7.92 kcal/mol, - 7.28 kcal/mol, - 7.19 kcal/mol and - 7.09 kcal/mol (top hit1-5) were found to have inhibitory activity against the ORF8-IRF3 complex. Molecular dynamics analysis of the complexes revealed the high compactness of residues, stable binding, and strong hydrogen binding network among the ORF8-nanotubes complexes. Moreover, the total binding free energy for top hit1-5 was calculated to be - 43.21 ± 0.90 kcal/mol, - 41.17 ± 0.99 kcal/mol, - 48.85 ± 0.62 kcal/mol, - 43.49 ± 0.77 kcal/mol, and - 31.18 ± 0.78 kcal/mol respectively. These results strongly suggest that the identified top five nanotubes (hit1-5) possess significant potential for advancing and exploring innovative drug therapies. This underscores their suitability for subsequent in vivo and in vitro experiments, marking them as promising candidates worthy of further investigation.

Biomass fly ash as nanofiller to improve the dielectric properties of low-density polyethylene for possible high-voltage applications.

Flexible capacitive energy storage applications require polymer nanocomposites with high dielectric properties, which can be accomplished by addition of inorganic nanofillers to the polymer matrix. Low-density polyethylene (LDPE), known for its good dielectric characteristics and wide use in electrical insulation have been investigated for the desired applications. However, the improvement of its breakdown strength still continues with the use of various nanomaterials employed as nanofillers. In this study, a waste-derived material known as biomass fly ash (BFA) as a nanofiller to improve the dielectric properties of LDPE has been explored. BFA exhibits versatility in its composition with various metal oxides, making it an attractive choice as a nanofiller. The BFA-LDPE sheets were prepared using a conventional solvent mixing and subsequent hot-pressing process, incorporating BFA loadings ranging from 1 % to 4 wt%. The effects of different BFA loadings were carefully examined, and the synthesized nanocomposites were extensively characterized using various characterization methods, such as XRD, SEM, FTIR, TGA and dielectric constant measurements, to investigate the crystallographic properties, morphology, chemical composition, and thermal stability. Among all the nanocomposites, 4 wt%BFA-LDPE exhibited the highest dielectric constant, with a value of 11.58, compared to simple LDPE that had a dielectric constant of 8.33. This improvement is ascribed to the synergistic effects of different inorganic metal oxides (SiO2, MgO, and Fe2O3) present in BFA. The results showed a significant enhancement in dielectric properties, indicating that the waste-derived BFA can be purposefully applied as an effective nanofiller in the LDPE-based composites with even less than 4% loading for electrical insulating applications in future studies.

Framework for the analysis of renewable energy grid policies in the context of COVID-19.

COVID-19 is a severe global pandemic that has caught the whole world unprepared. In the absence of a clear timeline for this pandemic to end, it is need of the hour to investigate the effect of this pandemic on both previous and anticipated investments. Global economic unrest has hindered the ramping deployment of Renewable energy projects. The most quick actions that may be taken to mitigate the effects and to up-rise the investment portfolio policies are a very critical tool in hands of government for a very immediate effect have also been made without keeping the context of COVID-19 into account. New variants of diff rent nature are being discovered and every now and then new lock downs are happening. In this context different policies have to be evaluated under the pandemic scenario. A case study of a large scale renewable energy project for a higher education institute in Pakistan is being used to measure the difference during COVID and pre COVID times. This paper provides a framework to investigate the impact of COVID on renewable energy system projects under current net-metering, net-billing and self-consumption policies. A recent investment in a photovoltaic system is assessed based on previously projected financial benefits versus the pandemic effected ones. This research concludes that investing in photovoltaic systems are still a viable option even in an extreme pandemic situation with less than 0.5 years increase in payback period, and the government can still provide a stimulus for investing in green energy by implementing net-metering policies on a larger scale.

Multi-Stressed Nano and Micro-Silica/Silicone Rubber Composites with Improved Dielectric and High-Voltage Insulation Properties.

The scope of silicone rubber (SiR) is confined due to the deprivation of its dielectric propertiesupon exposure to various ambient stresses. The aim of this research is to develop silicone rubber-based composites by employing inorganic oxide fillers for improved dielectric and high voltage insulation properties for widening its scope in the field of electrical appliances. This study reports the preparation of different composites of silicone rubber with varying concentrations of micro and nano-silica fillers. The dielectric propertytrends of these as-prepared neat and impregnated samples were examined via an indigenously developed weathering chamber capable of applying multiple stresses of acid rain, heat, humidity, UVA radiation, and salt fog. Dielectric constant values were measured before and after applying stresses. Upon applying stresses, a periodic decline in dielectric constant was observed. Improved dielectric properties were obtained by adding micro and nano-silica as fillers. A nano silica-incorporated silicone rubber product exhibited good potential for dual applications as dielectric and high voltage insulation.

Investigation of Hydrothermally Stressed Silicone Rubber/Silica Micro and Nanocomposite for the Coating High Voltage Insulation Applications.

Silicone rubber is a promising insulating material that has been performing well for different insulating and dielectric applications. However, in outdoor applications, environmental stresses cause structural and surface degradations that diminish its insulating properties. This effect of degradation can be reduced with the addition of a suitable filler to the polymer chains. For the investigation of structural changes and hydrophobicity four different systems were fabricated, including neat silicone rubber, a micro composite (with 15% micro-silica filler), and nanocomposites (with 2.5% and 5% nanosilica filler) by subjecting them to various hydrothermal conditions. In general, remarkable results were obtained by the addition of fillers. However, nanocomposites showed the best resistance against the applied stresses. In comparison to neat silicone rubber, the stability of the structure and hydrophobic behavior was better for micro-silica, which was further enhanced in the case of nanocomposites. The inclusion of 5% nanosilica showed the best results before and after applying aging conditions.