Immunoinformatics and Biophysics Approaches to Design a Novel Multi-Epitopes Vaccine Design against Staphylococcus auricularis

Due to the misuse of antibiotics in our daily lives, antimicrobial resistance (AMR) has become a major health problem. Penicillin, the first antibiotic, was used in the 1930s and led to the emergence of AMR. Due to alterations in the microbe’s genome and the evolution of new resistance mechanisms, antibiotics are losing efficacy against microbes. There are high rates of mortality and morbidity due to antibiotic resistance, so addressing this major health issue requires new approaches. Staphylococcus auricularis is a Gram-positive cocci and is capable of causing opportunistic infections and sepsis. S. auricularis is resistant to several antibiotics and does not currently have a licensed vaccine. In this study, we used bacterial pan-genome analysis (BPGA) to study S. auricularis pan-genome and applied a reverse immunology approach to prioritize vaccine targets against S. auricularis. A total of 15,444 core proteins were identified by BPGA analysis, which were then used to identify good vaccine candidates considering potential vaccine filters. Two vaccine candidates were evaluated for epitope prediction including the superoxide dismutase and gamma-glutamyl transferase protein. The epitope prediction phase involved the prediction of a variety of B-Cell and T-cell epitopes, and the epitopes that met certain criteria, such as antigenicity, immunogenicity, non-allergenicity, and non-toxicity were chosen. A multi-epitopes vaccine construct was then constructed from all the predicted epitopes, and a cholera toxin B-subunit adjuvant was also added to increase vaccine antigenicity. Three-dimensional models of the vaccine were used for downward analyses. Using the best-modeled structure, binding potency was tested with MHC-I, MHC-II and TLR-4 immune cells receptors, proving that the vaccine binds strongly with the receptors. Further, molecular dynamics simulations interpreted strong intermolecular binding between the vaccine and receptors and confirmed the vaccine epitopes exposed to the host immune system. The results support that the vaccine candidate may be capable of eliciting a protective immune response against S. auricularis and may be a promising candidate for experimental in vitro and in vivo studies.</jats:p

Immunoinformatics and Biophysics Approaches to Design a Novel Multi-Epitopes Vaccine Design against Staphylococcus auricularis

Due to the misuse of antibiotics in our daily lives, antimicrobial resistance (AMR) has become a major health problem. Penicillin, the first antibiotic, was used in the 1930s and led to the emergence of AMR. Due to alterations in the microbe&rsquo;s genome and the evolution of new resistance mechanisms, antibiotics are losing efficacy against microbes. There are high rates of mortality and morbidity due to antibiotic resistance, so addressing this major health issue requires new approaches. Staphylococcus auricularis is a Gram-positive cocci and is capable of causing opportunistic infections and sepsis. S. auricularis is resistant to several antibiotics and does not currently have a licensed vaccine. In this study, we used bacterial pan-genome analysis (BPGA) to study S. auricularis pan-genome and applied a reverse immunology approach to prioritize vaccine targets against S. auricularis. A total of 15,444 core proteins were identified by BPGA analysis, which were then used to identify good vaccine candidates considering potential vaccine filters. Two vaccine candidates were evaluated for epitope prediction including the superoxide dismutase and gamma-glutamyl transferase protein. The epitope prediction phase involved the prediction of a variety of B-Cell and T-cell epitopes, and the epitopes that met certain criteria, such as antigenicity, immunogenicity, non-allergenicity, and non-toxicity were chosen. A multi-epitopes vaccine construct was then constructed from all the predicted epitopes, and a cholera toxin B-subunit adjuvant was also added to increase vaccine antigenicity. Three-dimensional models of the vaccine were used for downward analyses. Using the best-modeled structure, binding potency was tested with MHC-I, MHC-II and TLR-4 immune cells receptors, proving that the vaccine binds strongly with the receptors. Further, molecular dynamics simulations interpreted strong intermolecular binding between the vaccine and receptors and confirmed the vaccine epitopes exposed to the host immune system. The results support that the vaccine candidate may be capable of eliciting a protective immune response against S. auricularis and may be a promising candidate for experimental in vitro and in vivo studies

Development of novel photoluminescent fibers from recycled polyester waste using plasma-assisted dyeing toward ultraviolet sensing and protective textiles

Polyester fibers have been applied in many industrial fields, such as plastic furniture, automotive parts, medical devices, and liquid crystal displays. However, polyester has been inherently resistant to dyeing owing to the absence of active staining sites. Herein, we present the preparation of new photoluminescent fibers starting from recycled polyester waste using plasma-assisted dyeing with the recyclable lanthanide-doped strontium aluminate nanoparticles. Nanostructured thin film of lanthanide-doped strontium aluminate nanoscale particles (3–8 nm) was immobilized onto polyester surface after plasma pretreatment, which generates reactive dyeing spots on the fibrous surface. Using photoluminescence spectra and CIE (Commission Internationale de L'éclairage) Lab parameters, the photoluminescent polyester fibers displayed various colors, including white in visible light and green under ultraviolet rays. After excitation at 382 nm, the photoluminescent thin layer on the fiber surface exhibited an emission peak of 439 nm. Various methods were utilized to inspect the morphology and elemental contents of the polyester fibers immobilized with phosphor nanoparticles. The superhydrophobicity of the phosphor-dyed polyester fibers was found to increase in direct proportion to the phosphor content, displaying improved sliding and static contact angles up to 155.8° and 8°, respectively. The results demonstrated that the dyed fibers had improved colorfastness, ultraviolet (UV) shielding, superhydrophobicity and antimicrobial activity. Both bending-length and air-permeability of dyed polyester fibers was evaluated to indicate good mechanical and comfort properties

Synthesis of designed new 1,3,4-oxadiazole functionalized pyrano [2,3-f] chromene derivatives and their antimicrobial activities

Diethyl 2-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)methylene)malonate (2) was synthesized from coumarin 1 and diethyl ethoxymethylene malonate in ethanol, followed by cyclization in diphenyl ether to give chromene-9-carboxylate (3). Sugar hydrazones 5a-c were formed by reacting hydrazide 4 with D-galactose, D-mannose, and D-xylose, then acetylated to per-O-acetyl derivatives 6a-c. Heating 5a-c with acetic anhydride at 100 °C gave oxadiazolines 7a-c. Compound 8, obtained by refluxing 4 with carbon disulfide, was alkylated to 9 or reacted to give 10. Further reactions yielded acetoxy derivative 13 and hydroxy derivative 14. Compounds 17a-e and 18a-e were synthesized using thiomorpholinophenyl ureido/thioureido-s-triazine. These compounds were characterized and evaluated for antibacterial activity against Gram (+ve) bacteria (B. subtilis, S. aureus) and Gram (-ve) bacteria (E. coli, P. aeruginosa) in addition to yeast-like fungi (C. albicans). Compounds 11, 13, 15, 16, 17c-e, and 18a-e showed the highest antibacterial activity. Molecular docking was performed to study their binding with transpeptidases

Measuring the Factors of Hesitancy in Saudi Population toward COVID-19 Vaccines

COVID-19 has major effects on the population, enforcing lockdowns and strict precautions across the world to deter the virus from spreading. The pandemic presents a significant threat to our health and well-being. As vaccines become available, COVID-19 lethality may be reduced by promoting widespread immunization. To achieve herd immunity thresholds for COVID-19, an estimated 70% of the population must be vaccinated. The public’s approval determines the success of the vaccination program. Understanding the factors that contribute to COVID-19 vaccine hesitancy is important. Therefore, this cross-sectional study was conducted on the Saudi population from all the regions of the Kingdom of Saudi Arabia to evaluate the level of knowledge about COVID-19 vaccines, estimate the turnout level for receiving the COVID-19 vaccine, and understand the reasons behind hesitancy toward COVID-19 vaccines. A total of 1,148 adults completed a web-based questionnaire, and the study tested several sociocultural and environmental variables that affect the community’s hesitancy toward vaccination. Results showed that gender characteristics had almost no effect on acceptance of the vaccination. Individuals of the younger age group &lt; 30 demonstrated an increase in the rate of vaccine hesitancy (53%) compared with individuals from the older age groups &gt; 40 (34.43%). In addition, middle and higher education groups were found to have significant vaccine hesitancy (77.4%) compared with the less educated group (41.1%). The most common concern among the non-vaccine takers in this questionnaire was that of vaccine safety: these participants believed the vaccine would result in health problems (49.3%), and most participants agreed (64%) that this was due to the insufficient duration of vaccine administration for safety evaluation.</jats:p

Synthetic approaches for novel fused pyrimidine derivatives: Design, structural characterization, antiviral, antitumor, and molecular docking evaluation

The goal of this work was to synthesize new compounds for anticancer evaluation as a trial to obtain new antitumor agents with higher activity and fewer side effects. Therefore, the precursor 2,2'-(1,4-phenylenebis (thiazole-4,2-diyl))bis (3-(dimethylamino)acrylonitrile) (4) was used to synthesize various azolopyrimidine derivatives connected to the thiazole moiety. Compounds 5–11, including pyrazolopyrimidine, triazolopyrimidine, and others, were produced by reacting enaminonitrile 4 with different N-nucleophiles. Additionally, compounds 12–15, such as isoxazole and pyrimidinethione derivatives, were obtained by reacting compound 4 with guanidine, hydrazine hydrate, hydroxylamine hydrochloride, and thiourea. Enaminonitrile 4 was also treated with barbituric acid, isoxazolone, and pyrazolone to yield pyranopyrimidine derivatives 18–20. Moreover, enaminonitrile 4 reacts with C-nucleophiles namely ''acetylacetone, dimedone, 2-cyanomethylbenzothiazole, and 2-cyanomethylbenzimidazole'' to give pyrano derivatives 21, 22 and fused pyridone derivatives 23 and 24, respectively. The cytotoxic activity of 20 novel compounds against HSV-1, HIV-1, and various cancer cell lines was assessed, with compounds 5, 7, and 9 showing the strongest effects. Molecular docking studies further evaluated the binding affinity of these derivatives, with docking scores ranging from −7.8679 to −8.3013 kcal/mol. Several new azolopyrimidine derivatives linked to the thiazole moiety were effectively synthesized and assessed in the study, and they showed notable cytotoxic activity against HSV-1, HIV-1, and several cancer cell lines

Design, synthesis, and structure–activity relationship of 2-chloro-3-formylquinoline containing hybrids as powerful antibacterial agents

This work aims to evaluate the antimicrobial activity of some new quinoline derivatives linked to pyrazole derivatives. The target compounds pyrazolylvinylquinoline 11a-g and 12a-g were achieved by the reaction of 2-chloro-6-nitro-3-quinolinecarboxaldehyde (4) with bromotriphenylphosphonylmethylpyrazole derivatives 9a,b to give the new quinoline derivatives 10a,b which in turn reacted with different aryl amines to afford 11a-g and 12a-g. Pyrazole derivatives 9a,b were obtained by the reaction of hydroxymethylpyrazole derivatives 8a,b with triphenylphosphine hydrobromide. Antimicrobial evaluation of the newly synthesized compounds showed that most of the new compounds appeared active toward Gram-positive bacteria more than Gram-negative bacteria. The biological evaluation of compounds 12d-g displayed the highest antimicrobial activity against the tested microorganism strains. Additionally, compounds 12d and 12f showed excellent activity against P. aeruginosa (MIC50 0.019 mg/mL), while compounds 11d, 11f, 12e, and 12g displayed good activity against the same microorganism (MIC50 0.07 mg/mL). On the other hand, most of the new compounds have moderate activity against E. coli. Compounds 12d and 12f showed excellent activity versus C. albicans in vitro antifungal activity (MIC50 0.15 mg/mL) comparing to or slightly lower than that of Fluconazole. Using molecular docking simulations, we evaluated the binding affinities and interactions of four chosen derivatives 12d-g with a target PDB code 3WT0 protein