Nanosponges: As a Dynamic Drug Delivery Approach for Targeted Delivery

Recent advancements in nanotechnology have resulted in improved medicine delivery to the target site. Nanosponges are three-dimensional drug delivery systems that are nanoscale in size and created by cross-linking polymers. The introduction of Nanosponges has been a significant step toward overcoming issues such as drug toxicity, low bioavailability, and predictable medication release. Using a new way of nanotechnology, nanosponges, which are porous with small sponges (below one microm) flowing throughout the body, have demonstrated excellent results in delivering drugs. As a result, they reach the target place, attach to the skin's surface, and slowly release the medicine. Nanosponges can be used to encapsulate a wide range of medicines, including both hydrophilic and lipophilic pharmaceuticals. The medication delivery method using nanosponges is one of the most promising fields in pharmacy. It can be used as a biocatalyst carrier for vaccines, antibodies, enzymes, and proteins to be released. The existing study enlightens on the preparation method, evaluation, and prospective application in a medication delivery system and also focuses on patents filed in the field of nanosponges.Copyright © 2023 The Authors.

Structure-Based Identification and Analysis of Viral Protease Inhibitors Targeting SARS CoV-2 Virus Replication

The re-emergence of SARS-CoV, known as SARS-CoV-2, has proven extremely infectious that has infected a huge population worldwide. SARS-CoV-2 genome is translated into polyproteins that is processed by virus-specific protease enzymes. 3CLprotease is named as the main protease (Mpro) enzyme that cleaves nsp4 to nsp16. This crucial role of Mpro makes this enzyme a prime and promising antiviral target. Till date, there is no effective commercially available drug against COVID-19 and launching a new drug into the market is a complicated and time-consuming process. Therefore, drug repurposing is a new but familiar approach to reduce the time and cost of drug discovery. We have used a high-throughput virtual screening approach to examine FDA approved library, natural compound library, and LOPAC 1280 (Library of Pharmacologically Active Compounds, Sigma-Aldrich, St. Louis, MO) library against Mpro. Primary screening identified potential drug molecules for the target, among which ten molecules were studied further using biophysical and biochemical techniques. SPR was used to validate the binding of inhibitors to purified Mpro and using FRET-based biochemical protease assay these inhibitors were confirmed to have Mpro inhibitory activity. Based on the kinetic studies, the antiviral efficacy of these compounds was further analysed by cell-culture based antiviral assays. Four out of ten molecules inhibited SARS-CoV-2 replication in Vero cells at a concentration range of 12.5 to 50 muM. The antiviral activity was evaluated by RT-PCR assay and TCID50 experiments. The co-crystallization of Mpro in complex with inhibitor for determining their structures is being carried out. Collectively, this study will provide valuable mechanistic and structural insights for development of effective antiviral therapeutics against SARS-CoV-2.

Polymerization of Allyltrimethylisilane and 4-Methyl-1-Pentene by Using Metallocene Catalysts.

Polymers of higher olefin, obtained by Ziegler-type polymerization, have been used in some critical fields, e.g., as the membrane for extracorporeal membrane oxygenation (ECMO), which plays an important role in the treatment of patients with severe COVID-19. The polymer obtained by a single-site catalyst, e.g., metallocene catalysts, demonstrated a higher performance. The homo- and co-polymerization of allyltrimethylisilane (ATMS) and 4-methyl-1-pentene (4M1P) were conducted using syndiospecific (cat 1) and isospecific (cat 2) metallocene catalysts. Cat 1 showed low conversions and provided a polymer with a higher molecular weight, while cat 2 behaved oppositely. 13C-NMR spectra certified the stereotacticity of the resultant polymer, and the resonance of the carbon atom of CH2 (αα') between the two tertiary carbon atoms of the ATMS and 4M1P units were observed. This could be the evidence of the formation of a true copolymer. The crystallization of the polymer was explored using a differential scanning calorimeter (DSC) and wide angle X-ray diffraction (WAXD). All homopolymers and some of the copolymers showed high melting temperatures and low melting enthalpies. The WAXD patterns of the syndiotactic polymer and isotactic homopolymer or the ATMS-rich copolymer were consistent with the reported literature, but the isotactic 4M1P-rich copolymer provided the crystal form I, which is unusual for a 4M1P polymer without any pretreatment.

Design spherical particles of potassium peroxymonosulfate compound salt with high stability and good powder properties via an agglomeration-dissolution mechanism

With the outbreak of COVID-19, disinfection protection has become a necessary measure to prevent infection. As a new type of disinfectant, potassium peroxymonosulfate compound salt (PMS) has the advantages of good bactericidal effect, non-toxicity, high safety and stability. However, the current PMS products with irregular particle shapes lead to poor flowability, high hygroscopicity, poor stability of reactive oxygen species (ROS) and serious caking problems. In this work, an agglomeration-dissolution mechanism was designed to prepare spherical PMS particles with large size (>300 mm) and high sphericity (up to 90%), effectively addressing the above problems. Shaping (dissolution and abrasion) is the key to improving sphericity, which is mainly controlled by the design of the heating mode, residence time and stirring rate. Compared with the irregular PMS particles, the large spherical particles present better flowability (angle of repose decreased by 35.80%, Carr's index decreased by 64.29%, Hausner's ratio decreased by 19.14%), lower hygroscopicity (decreased by 38.0%), lower caking ratio (decreased by 84.50%), and higher stability (the monthly loss of ROS was reduced by 61.68%). The agglomeration -dissolution mechanism demonstrates the crystallization, agglomeration, dissolution and abrasion pro-cess of inorganic salt crystals, providing an opportunity to prepare high-end inorganic crystal materials with high-quality morphologies.(c) 2022 Chinese Society of Particuology and Institute of Process Engineering, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

A new short synthesis route for favipiravir and its analogue: Their tautomerization behaviour

The study of tautomerism in biologically relevant heterocycles is essential, as it directly affects their chemical properties and biological function. Lactam-lactim tautomerization in pyridine/pyrazine derivatives is such a phenomenon. Favipiravir, a pyrazine derivative, is an essential antiviral drug molecule having notable performance against SARS-CoV-2. Along with a better yielding synthetic method for favipiravir, we have also investigated the lactam-lactim tautomerization of favipiravir and its analogous molecules. Most of these molecules were crystalized and studied for various interactions in their lattice. Many interesting supramolecular interactions such as hydrogen bonding, pi-pi stacking and halogen bonding were revealed during the analysis. Some of these structures show interesting F-F halogen bonding and water channels in their solid state.Copyright © 2022 The Royal Society of Chemistry.

Modified Synthesis and Isolation of an Advanced Intermediate of Remdesivir

Synthesis and isolation of an advanced intermediate (S)-2-Ethylbutyl 2-(((S)-(4-nitrophenoxy) (phenoxy) phosphoryl) amino) propanoate (1b), which is being used for the manufacture of the prodrug diastereoisomer 1d called Remdesivir have been carried out in high yield with efficient stereoselectivity. The isolated advanced intermediate 1b was a dia-stereoselective nucleoside phosphoramidate prodrug used as an antiviral agent having a mix-ture of two (SS) and (SR) diastereomers with stereocenter at phosphorus, which was purified by converting into a more stable diastereoselective isomer (SS) by simple physical fractional crystallization process, resulting in an improved yield of ~45%. The recrystallization has been afforded diastereomerically in 99% pure (SS)-isomer 1b. The 1H NMR characterization data confirm the (SS)-isomer (1b). The developed process holds significant potential for large-scale reactions relatively with commercially available low-cost solvents and co-solvents, resulting in an alternative cheaper process. © 2022 Bentham Science Publishers.

Low-Dimensional Compounds Containing Bioactive Ligands. Part XX: Crystal Structures, Cytotoxic, Antimicrobial Activities and DNA/BSA Binding of Oligonuclear Zinc Complexes with Halogen Derivatives of 8-Hydroxyquinoline

Two tetranuclear [Zn4Cl2(ClQ)6]·2DMF (1) and [Zn4Cl2(ClQ)6(H2O)2]·4DMF (2), as well as three dinuclear [Zn2(ClQ)3(HClQ)3]I3 (3), [Zn2(dClQ)2(H2O)6(SO4)] (4) and [Zn2(dBrQ)2(H2O)6(SO4)] (5), complexes (HClQ = 5-chloro-8-hydroxyquinoline, HdClQ = 5,7-dichloro-8-hydroxyquinoline and HdBrQ = 5,7-dibromo-8-hydroxyquinoline) were prepared as possible anticancer or antimicrobial agents and characterized by IR spectroscopy, elemental analysis and single crystal X-ray structure analysis. The stability of the complexes in solution was verified by NMR spectroscopy. Antiproliferative activity and selectivity of the prepared complexes were studied using in vitro MTT assay against the HeLa, A549, MCF-7, MDA-MB-231, HCT116 and Caco-2 cancer cell lines and on the Cos-7 non-cancerous cell line. The most sensitive to the tested complexes was Caco-2 cell line. Among the tested complexes, complex 3 showed the highest cytotoxicity against all cell lines. Unfortunately, all complexes showed only poor selectivity to normal cells, except for complex 5, which showed a certain level of selectivity. Antibacterial potential was observed for complex 5 only. Moreover, the DNA/BSA binding potential of complexes 1–3 was investigated by UV-vis and fluorescence spectroscopic methods.

Photocatalytic Degradation of Paracetamol under Simulated Sunlight by Four TiO2 Commercial Powders: An Insight into the Performance of Two Sub-Micrometric Anatase and Rutile Powders and a Nanometric Brookite Powder

The photocatalytic degradation of the emerging contaminant paracetamol in aqueous solution has been studied under 1 SUN (~1000 W m−2) in the presence of four commercial TiO2 powders, namely sub-micrometric anatase and rutile, and nanometric brookite and P25 (the popular anatase/rutile mixture used as a benchmark in most papers). The rutile powder showed low activity, whereas, interestingly, the anatase and the brookite powders outperformed P25 in terms of total paracetamol conversion to carboxylic acids, which, according to the literature, are the final products of its degradation. To explain such results, the physicochemical properties of the powders were studied by applying a multi-technique approach. Among the physicochemical properties usually affecting the photocatalytic performance of TiO2, the presence of some surface impurities likely deriving from K3PO4 (used as crystallization agent) was found to significantly affect the percentage of paracetamol degradation obtained with the sub-micrometric anatase powder. To confirm the role of phosphate, a sample of anatase, obtained by a lab synthesis procedure and having a "clean” surface, was used as a control, though characterized by nanometric particles and higher surface area. The sample was less active than the commercial anatase, but it was more active after impregnation with K3PO4. Conversely, the presence of Cl at the surface of the rutile did not sizably affect the (overall poor) photocatalytic activity of the powder. The remarkable photocatalytic activity of the brookite nanometric powder was ascribed to a combination of several physicochemical properties, including its band structure and nanoparticles size.

DEVELOPMENT AND EVALUATION OF FAVIPIRAVIR AGGLOMERATES FOR DIRECT COMPRESSION BY CRYSTALLO-CO-AGGLOMERATION TECHNIQUE

During the severe worldwide pandemic caused due to SARS COV-2 Corona virus, Favipiravir has been used for the treatment. It is a water insoluble anti-viral drug with poor dissolution and poor flow properties, resulting in poor oral absorption and less bioavailability. For a long time, the phrase "direct compression" was used to describe the compression of a single crystalline component into a compact without the addition of any other materials. Using excipients and solvents, the crystallo-co-agglomeration process aggregates drug crystals in the form of small spherical particles to create an intermediate product with better micromeritic and mechanical characteristics, solubility, and dissolution. Crystallo-co-agglomeration is a unique approach in which the pharmaceuticals or excipients are crystallized and agglomerated concurrently from a good solvent and/or bridging liquid by adding a non-solvent. The present study aims to formulate crystallo-co-agglomerates of Favipiravir to improve its physicochemical and mechanical properties. Results obtained during the evaluation showed that CCA technique could be successfully employed as an alternative to conventional wet agglomeration.

Interaction of GC376, a SARS-COV-2 MPRO inhibitor, with model lipid membranes

Partitioning and effect of antiviral GC376, a potential SARS-CoV-2 inhibitor, on model lipid membranes was studied using dynamic light scattering (DLS), UV–VIS spectrometry, Excimer fluorescence, Differential scanning calorimetry (DSC) and Small- and Wide-angle X-ray scattering (SAXS/WAXS). Partition coefficient of GC376 between lipid and water phase was found to be low, reaching KP = 46.8 ± 18.2. Results suggest that GC376 partitions into lipid bilayers at the level of lipid head-groups, close to the polar/hydrophobic interface. Changes in structural and thermodynamic properties strongly depend on the GC376/lipid mole ratio. Already at lowest mole ratios GC376 induces increase of lateral pressures, mainly in the interfacial region of the bilayer. Hereby, the pre- and main-transition temperature of the lipid system increases, what is attributed to tighter packing of acyl chains induced by GC376. At GC376/DPPC ≥ 0.03 mol/mol we detected formation of domains with different GC376 content resulting in the lateral phase separation and changes in both, main transition temperature and enthalpy. The observed changes are attributed to the response of the system on the increased lateral stresses induced by partitioning of GC376. Obtained results are discussed in context of liposome-based drug delivery systems for GC376 and in context of indirect mechanism of virus replication inhibition.

Burnout, Depression, Anxiety, and Stress among Family Physicians in Kansas: 18 Months into the COVID-19 Pandemic

Introduction: Given the significant turmoil during the COVID-19 pandemic, the authors evaluated burnout and other types of emotional distress experienced by family physicians in Kansas during the second year of the pandemic. The authors compared findings of this study to a similar study conducted 3 months into the pandemic. Method(s): A cross-sectional online survey of 272 actively practicing family physicians in Kansas was conducted from September 15 to October 18, 2021. A 34-item questionnaire was used to measure the physicians' levels of burnout, personal depression, anxiety, and stress. A mixed method approach was used to collect, analyze, and interpret the data. Descriptive statistics, Mann-Whitney U test/independent samples t-test, v2, adjusted odds ratio, and immersion-crystallization methods were used to analyze the data. Result(s): The response rate was 48.9% (n = 133). In aggregate, 69.2% of respondents reported at least 1 manifestation of professional burnout in 2021 compared with 50.4% in 2020;P <= .01). The 2021 respondents were at higher odds of experiencing burnout compared with 2020 respondents (aOR = 1.86;95% CI, 1.00 to 3.57;P = .046). The respondents who reported at least 1 manifestation of professional burnout were more likely to screen positive for depression (aOR = 1.87;95% CI, 1.31-2.66;P <= .01), report higher levels of anxiety (aOR = 1.53;95% CI, 1.04-2.24;P = .013), and higher levels of stress (aOR = 1.39;95% CI, 1.17-1.66;P <= .001). Conclusion(s): As the COVID-19 pandemic continued, there are significant and worsening rates of professional burnout and other forms of emotional distress among family physicians. These findings suggest timely need for appropriate psychological supports. Copyright © 2022 American Board of Family Medicine. All rights reserved.

Toward the Discovery of SARS-CoV-2 Main Protease Inhibitors: Exploring Therapeutic Potentials of Evodiamine and Its Derivatives, Virtual Screening, Molecular Docking, and Molecular Dynamic Studies

Continuous scientific research is necessary to help in the discovery of new promising remedies for the treatment of COVID-19, caused by the SARS-CoV-2 virus. This current research was aimed at identifying potential novel inhibitors of the SARS-CoV-2 main protease, which represents one of the most important targets in the viral life cycle. Protein data bank file ID: 7JQ2 was used containing the co-crystallized inhibitor MPI5 with the Main protease. A virtual screening process for natural evodiamine compounds was performed through absorption, distribution, metabolism, elimination, and toxicity studies, and the promising hits were docked into the binding site of the enzyme. 13-(4-Chlorobenzoyl)-10-hydroxy-14-methyl-8,13,13b,14-tetrahydroindolo[2',3':3,4]pyrido[2,1-b]-quinazolin-5(7H)-one (29) interacted favorably with the enzyme;it showed high similarity to MPI5. Molecular dynamic simulations for 29 proved the stability of its binding to SARS-CoV-2 protease over 100 ns;subsequent MMGBSA analysis also supported this principle. Furthermore, 29 elucidated higher limiting action on enzymatic behavior throughout the whole process when compared to MPI5. This provides sufficient evidence for the potential of evodiamine compounds in modern antiviral research, especially compound 29, against the modern COVID-19 pandemic. Copyright © The Author(s) 2022.

Poly(lactic acid)/Poly(vinyl alcohol) Biodegradable Blends Using Monobutyl Maleate as a Plasticizer and Compatibilizer

The Covid-19 pandemic situation has contributed to sparking discussions about an increase in packaging combined with the nonrecommendation of reuse. For this reason, many countries have encouraged the use of biodegradable polymers. In this study, blends of poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVAL) were prepared at 80/20 (w/w) in the presence of specific amounts of monobutyl maleate (MBM) as a compatibilizer. All of these components are proven biodegradable. PLA/ PVAL/MBM blend films were obtained by thermopressing, and the thermal, mechanical, and morphological properties were evaluated by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), tensile tests, stress relaxation, and scanning electron microscopy (SEM). DSC results suggest that MBM can act as a plasticizer, at least for the PLA matrix, reducing the Tg from 60.2 degrees C (without MBM) to 23.5 degrees C in the case of the highest quantity of plasticizer (20%). Due to increase in macromolecular mobility, MBM also affects PLA crystallization. As a consequence of brittleness of the other samples, only those containing 15 and 20% of MBM (in PLA basis) did not fail the tensile and relaxation tests, showing more than 25% of elongation at break. Both the elastic and viscous parameters and the equilibrium modulus (Eeq) of the Maxwell-Wiechert mechanical system show lower values for the sample with higher MBM content. The SEM images show that the presence of the compatibilizer improves the adhesion between the PLA-rich phase and PVAL-rich phase.

Design spherical particles of potassium peroxymonosulfate compound salt with high stability and good powder properties via an agglomeration-dissolution mechanism

With the outbreak of COVID-19, disinfection protection has become a necessary measure to prevent infection. As a new type of disinfectant, potassium peroxymonosulfate compound salt (PMS) has the advantages of good bactericidal effect, non-toxicity, high safety and stability. However, the current PMS products with irregular particle shapes lead to poor flowability, high hygroscopicity, poor stability of reactive oxygen species (ROS) and serious caking problems. In this work, an agglomeration-dissolution mechanism was designed to prepare spherical PMS particles with large size (>300 μm) and high sphericity (up to 90%), effectively addressing the above problems. Shaping (dissolution and abrasion) is the key to improving sphericity, which is mainly controlled by the design of the heating mode, residence time and stirring rate. Compared with the irregular PMS particles, the large spherical particles present better flowability (angle of repose decreased by 35.80%, Carr's index decreased by 64.29%, Hausner's ratio decreased by 19.14%), lower hygroscopicity (decreased by 38.0%), lower caking ratio (decreased by 84.50%), and higher stability (the monthly loss of ROS was reduced by 61.68%). The agglomeration-dissolution mechanism demonstrates the crystallization, agglomeration, dissolution and abrasion process of inorganic salt crystals, providing an opportunity to prepare high-end inorganic crystal materials with high-quality morphologies. © 2022 Chinese Society of Particuology and Institute of Process Engineering, Chinese Academy of Sciences

A new diagnosis of monoclonal B-cell lymphocytosis with cytoplasmic inclusions in a patient with COVID-19

A 75-year-old man with a history of chronic ischemic heart disease with a previously normal blood count, presented to the emergency room with fever and tachycardia. There was no hepatosplenomegaly or lymphadenopathy. An electrocardiogram showed left bundle branch block. Because of the fever the patient underwent SARS-CoV-2 RNA testing with positive result. The patient's blood count showed a WBC of 10.46 x 109/L, lymphocytes 4.51 x 109/L, hemoglobin 129 g/ L, and platelet count 233 x 109/L. D-Dimer was 659 mug/L (normal range <500) and IL6 was 76.3 pg/ml (normal range <6.4). A computed tomography scan of the chest showed bilateral interstitial infiltrates associated with multiple enlarged mediastinal lymph nodes. Following a rapid and unexpected increase of the WBC to 17.49 x 109/L with lymphocyte count of 8.37 x 109/L, a blood film and immunotyping were performed. The film showed small/medium sized lymphocytes, with a variable N: C ratio and moderately basophilic cytoplasm. Smear cells were present. About 25% of the lymphocytes showed the negative images of one to three rodshaped crystals (average 2 per cell). Some immature monocytes and neutrophils showed mild toxic granulation or abnormal nuclear shapes, consistent with COVID-19. Flow cytometric immunotyping showed an increased number of circulating B cells (93% of lymphocytes, 7.78 x 109/L) with lambda light chain restriction and expressing CD19, CD5, CD23, weak CD20, CD43, and CD200;CD10, CD79b, CD81, FMC7, and CD38 were negative. At this stage the clinical picture could not be distinguished from chronic lymphocytic leukemia (CLL). Two months later the WBC and lymphocyte count returned to normal and immuno typing showed only 0.63 x 109/L CD5-positive clonal B cells. Lymphocytes with cytoplasmic crystals were still present. A diagnosis of monoclonal B-cell lymphocytosis (MBCL) was made. Patients with CLL in whom COVID-19 led to a marked but transient increase in the lymphocyte count have been reported. In our case, COVID-19 in a patient with MBCL led to an increase in the lymphocyte count simulating CLL but follow-up indicated the correct diagnosis. We report here the observation of endocellular crystals, attributable to crystallization of immunoglobulin, in MCBL, a phenomenon previously reported in CLL.

AKI in COVID-19 Infection: Role of Hypercatabolic Status

Introduction: Acute Kidney Injury (AKI) is a very common complication of patients with SARS-COV-2 virus (COVID-19) infection. COVID-19 infected patients have longer hospital length of stays and higher mortality rate. There are multiple postulated mechanisms for AKI in the setting of COVID-19. Some researchers reported that the COVID-19 virus directly binds to the ACE-2 receptors in proximal tubules and leads to tubular dysfunction. In rare cases, a hypercatabolic state can be seen that carries a significantly higher mortality rate with ensuing hyperuricemia and hyperphosphatemia. Case Description: We describe a patient presenting with severe AKI with hypercatabolic state in the setting of COVID-19 infection. 40 year old male with a history of hypertension and CHF (EF 35%) presented with fatigue, diarrhea, nausea and vomiting for 10 days after COVID-19 infection. He was found to have severe AKI with blood urea nitrogen of 254 and creatinine of 21 mg/dl which was associated with hyperkalemia, gap acidosis, severe hyperuricemia (23 mg/dl) and hyperphosphatemia (17 mg/dl). Despite aggressive volume resuscitation in the ICU, the patient remained oliguric with no improvement in kidney function for two days. He was subsequently initiated on hemodialysis. After getting 2 sessions of dialysis without ultrafiltration, renal recovery was noted eventually normalizing within 10 days. Extensive work up indicated the patient had no tumor lysis syndrome and rhabdomyolysis on this admission. Discussion(s): There are multifactorial mechanisms for AKI in patients with COVID-19 infection including direct viral invasion of the kidney proximal tubules. Our case demonstrated that a hypercatabolic state may contribute to AKI in these patients. The proposed mechanisms involve elevated serum uric acid levels causing small renal arterial constriction, glomerular auto-dysregulation and tubular crystallization due to supersaturation causing to kidney tubular injury. Thus, clearance of uric acid and phosphorus with dialysis may promote more rapid kidney function recovery.

Rapid synthesis of bismuth-organic frameworks as selective antimicrobial materials against microbial biofilms.

Antibiotic resistance is a global public health threat, and urgent actions should be undertaken for developing alternative antimicrobial strategies and approaches. Notably, bismuth drugs exhibit potent antimicrobial effects on various pathogens and promising efficacy in tackling SARS-CoV-2 and related infections. As such, bismuth-based materials could precisely combat pathogenic bacteria and effectively treat the resultant infections and inflammatory diseases through a controlled release of Bi ions for targeted drug delivery. Currently, it is a great challenge to rapidly and massively manufacture bismuth-based particles, and yet there are no reports on effectively constructing such porous antimicrobial-loaded particles. Herein, we have developed two rapid approaches (i.e., ultrasound-assisted and agitation-free methods) to synthesizing bismuth-based materials with ellipsoid- (Ellipsoids) and rod-like (Rods) morphologies respectively, and fully characterized physicochemical properties. Rods with a porous structure were confirmed as bismuth metal-organic frameworks (Bi-MOF) and aligned with the crystalline structure of CAU-17. Importantly, the formation of Rods was a 'two-step' crystallization process of growing almond-flake-like units followed by stacking into the rod-like structure. The size of Bi-MOF was precisely controlled from micro-to nano-scales by varying concentrations of metal ions and their ratio to the ligand. Moreover, both Ellipsoids and Rods showed excellent biocompatibility with human gingival fibroblasts and potent antimicrobial effects on the Gram-negative oral pathogens including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. Both Ellipsoids and Rods at 50 â€‹µg/mL could disrupt the bacterial membranes, and particularly eliminate P. gingivalis biofilms. This study demonstrates highly efficient and facile approaches to synthesizing bismuth-based particles. Our work could enrich the administration modalities of metallic drugs for promising antibiotic-free healthcare.

Online Education in Children During COVID-19 Pandemic

The Corona pandemic led to the closure of schools and educational institutions and limited access to education for children. Therefore, the educational approach has changed to e-learning. E-learning has advantages and disadvantages, among which the nursing advocate is crystallized. Inclusive development of education is not possible in all places, and this has challenged educational justice. Another important issue is the challenge of children with special needs during a pandemic. These children are exposed to many problems with the closure of educational centers and less visits to health centers. These challenges require careful planning and special attention to this group of children to minimize the adverse consequences of the disease on children.

Mutation Pattern in the Receptor Binding Motif of SARS-Cov-2 Variants and the Effect on Molecular Interactions in Docked Ligand Complexes

The spike glycoprotein of SARS-Cov-2 is a therapeutic target for Covid-19 and mutations in the Receptor Binding Motif (RBM) may alter the binding properties of ligands proposed to inhibit viral entry. This study aimed to identify the existence of a mutation pattern in the RBMs of SARS-Cov-2 variants and study the effect on ligand binding interactions. RBM sequences were obtained using NCBI BLASTP and subjected to multiple and pairwise sequence alignment analysis. Hypothetical generations were drawn from the phylogenetic tree. The effect of mutation on ligand binding was studied by docking zafirlukast on selected RBMs. Molecular dynamics simulations were conducted to explain molecular interactions. The sequences at the same phylogenetic level showed higher similarity with the observed differences defined by the crystallized chain length. 6XDG_E, a leaf node sequence was 76% similar to 7NXA_E, a branch from the root, and had the highest mutation. Differences in sequence similarity across successive generations were based on mutations and crystallized chain length and the amino acid substitution is not predictable. Different bond types and binding affinities were observed as well as varying Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), and Region of Gyration (RoG) values for the RBMs in different variants. The RMSD, RMSF, and RoG did not differ significantly in the bound and free states of RBM from specific variants suggesting that the observed differences are attributable to amino acid substitutions. This information is crucial for drug development intended to block SARS-Cov-2 entry.