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The approval of mRNA vaccine technique against COVID-19 opens a door to research and the creation of new drugs against different infectious pathologies or even cancer, since for several diseases the therapeutic options are limited, and different viral diseases are treated only symptomatically. For these reasons, this study proposed a hypothesis supported by biological studies, that it provides a theoretical basis for the possible development of a drug that used the mRNA technique and the ribonucleolytic action of a ribonuclease for a possible antiviral therapy, and analyzed a future perspective of this technique in order to provide a bibliographic basis on this hypothesis and motivate researchers to carry out biological studies on this topic.Copyright © 2022, Health Biotechnology and Biopharma. All rights reserved.
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Novel safe and stable teracationic Zinc phthalocyanine is efficient against bacteria, fungi and viruses also under indoor light Recently a novel photosensitizer with outstanding properties, phthalocyanine LASU has being developed. The compound possesses unprecedented stability and antimicrobial activity. It can be activated by a weak indoor light of 270 lux and shows the activity against G+ and G- bacteria as well as fungi and viruses. Over 3 log inactivation of bacteria and fungi on the surface of a LASU-impregnated material can be achieved in 1/2-1 h of illumination with a regular indoor and/or natural light. A cotton filter impregnated with 0.1 g/m2 of LASU eradicates on its surface the coronavirus HCoV-229E by 3.5 log in 30 minutes under indoor/natural light of 500 lux. The molecule is photostable and remains active for weeks with no significant bleaching. Another remarkable property is its ability to bind to cellulose support. It readily attaches to a fiber substrate through electrostatic interactions, moreover, the size of LASU ring matches the pitch of cellulose polymer, making the conjugate unusually strong. Hence the compound does not leech to water and is stable against temperature and surfactants. The toxicology studies also reveals that substance is non-irritating for human skin, and is non-mutagenic, which makes it suitable for human-wearable items.Copyright © 2023
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Background: In order to propose a destination for the bottom ash generated from biomass burning, its morphology, functional groups and mineral phases were studied. Dipyrone has been extensively used as an antipyretic, increased due to cases of COVID-19, and due to excretion by urine, incorrect disposal and industrial effluents has been destined to wastewater, being harmful to human and animal life. The present study proposes using biomass ash for the adsorption of dipyrone. Result(s): The characterization of biomass ash shows a sufficient surface area size for adsorption, and a mainly amorphous structure with some peaks of quartz, calcite and other mineral phases. The results show that the kinetic model which best describes the adsorption is the pseudo-first-order model. The Langmuir model best fits at 25 degreeC, and the Freundlich model best describes the adsorption at 35 and 45 degreeC. The thermodynamic parameters indicated that the process is endothermic with a maximum adsorptive capacity of 65.27 mg g-1. In addition, the adsorption is spontaneous, disordered and chemical. The ionic strength study reveals that the adsorbent is promising for real effluent treatment and there is evidence that electrostatic interaction is not the primary adsorptive mechanism, agreeing with the result obtained from pH testing. The proposed mechanism for dipyrone removal involves hydrogen bonds, pi bonds and electron donor-acceptor complex. Conclusion(s): The results are promising in comparison with recent literature and solve two environmental problems: biomass bottom ash disposal and pharmaceutical removal in aqueous medium. The ash may be regarded as a low-cost and environmentally friendly adsorbent. © 2023 Society of Chemical Industry (SCI).
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Polypropylene mesh, integrated in N95 respirators and surgical masks that are widely used in the current crisis of COVID-19, filters aerosols via electrostatics in addition to the physical block. However, any contact to water such as storage under high humidity, exposure to exhaling breath, and washing in water removes its charges and thus compromises its filtering efficiency. We developed a desk top device based on a Cockcroft-Walton's voltage multiplier that can restore the electrostatic charge of surgical masks within 1 min and recover the filtering efficiency of the polypropylene mesh from 87% to 97%. The device is easy to operate and safe, thus may be applied for the reuse of surgical masks towards reducing the plastic wastes.
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Background: Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has given rise to COVID-19 pandemic, which has become a wreaking havoc worldwide. Therefore, there is an urgent need to find out novel drugs to combat SARS-CoV-2 in-fection. In this backdrop, the present study aimed to assess potent bioactive compounds from different fungi as potential inhibitors of SARS-CoV-2 main protease (Mpro) using an in-silico analysis. Method(s): High-Resolution Liquid Chromatography Mass Spectrometry analysis (HR-LCMS) was used for the bioactive profiling of ethanolic crude extract of Dictyophora indusiata, Geastrum tri-plex and Cyathus stercoreus. Of which, only bergenin (D. indusiata), quercitrin (G. triplex) and di-hydroartemisinin (C. stercoreus) were selected based on their medicinal uses, binding score and the active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 Mpro, was docked with bergenin, quercitrin and dihydroartemisinin using Autodock 4.2. Result(s): A total of 118 bioactive compounds were analyzed from the crude extract of used fungi and identified using HR LC/MS analysis. The binding energies obtained were-7.86,-10.29 and-7.20 kcal/mol, respectively, after docking analysis. Bergenin, quercitrin and dihydroartemisinin formed hydrogen bond, electrostatic interactions and hydrophobic interactions with foremost active site amino acids THR190, GLU166, GLN189, GLY143, HIS163, HIS164, CYS145 and PHE140. Conclusion(s): Present investigation suggests that these three compounds may be used as alternative inhibitors against SARS-CoV-2 Mpro. However, further research is necessary to assess in vitro potential of these compounds. To the best of our knowledge, the present investigation reported these three bioactive compounds of fungal origin for the first time.Copyright © 2021 Bentham Science Publishers.
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This study aims to fill a knowledge gap in our understanding of Omicron variant receptor-binding domain (RBD) interactions with host cell receptor, angiotensin-converting enzyme 2 (ACE2). Protein-protein docking, scoring, and filtration were all performed using the HDOCK server. A coarse-grained prediction of the changes in binding free energy caused by point mutations in Omicron RBD was requested from the Binding Affinity Changes upon Mutation (BeAtMuSiC) tools. GROMACS was utilized to perform molecular dynamics simulations (MD). Within the 15 mutations in Omicron RBD, several mutations have been linked to increased receptor affinity, immunological evasion, and inadequate antibody response. Wild-type (wt) SARS-CoV-2 and its Omicron variant have 92.27% identity. Nonetheless, Omicron RBD mutations resulted in a slight increase in the route mean square deviations (RMSD) of the Omicron structural model during protein-protein docking, as evidenced by RMSDs of 0.47 and 0.85 A for the wt SARS-CoV-2 and Omicron RBD-ACE2 complexes, respectively. About five-point mutations had essentially an influence on binding free energy, namely G6D, S38L, N107K, E151A, and N158Y. The rest of the mutations were expected to reduce the binding affinity of Omicron RBD and ACE2. The MD simulation supports the hypothesis that Omicron RBD is more stably bound to ACE2 than wt SARS-CoV-2 RBD. Lower RMSD and greater radius of gyration (Rg) imply appropriate Omicron structure 3D folding and stability. However, the increased solvent accessible surface area (SASA) with a greater Omicron shape may have a different interaction with receptor binding and regulate virus entrance. Omicron RBD's mutations help it maintain its structural stability, compactness, ACE2 binding, and immune evasion.Copyright © 2022 AEPress, s.r.o.. All rights reserved.
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In this work, an analysis has been done to describe the molecular structure, spectroscopic, reduced density gradient, topological properties, atomic charges, Lipinski rule, Natural bond orbital analysis, docking and molecular dynamics simulation of the potent antiviral drug EIDD-2801 in the effective treatment against COVID-19. Intramolecular charge distribution is well understood by three schemes such as AIM, Mulliken and NBO analysis and non-covalent interactions have been understood through reduced density gradient. Topological properties, such as charge density and Laplacian of charge density along with the electron localization function, make it easy to obtain comprehensive information about bond strengths and critical points. The details obtained from the calculation of global reactivity descriptors and Lipinski rule are useful for understanding the nature of molecular reactivity and site selectivity. Electrostatic potentials help to identify potential electrophilic and nucleophilic sites for interaction between EIDD-2801 and target proteins. The molecular docking combined with molecular dynamic simulation studies enables us to get better picture about the ligand-protein interaction.Copyright © 2023 Indian Chemical Society
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Touchless technology has garnered significant interest in recent years because of its effectiveness in combating infectious diseases such as the novel coronavirus (COVID-19). The goal of this study was to develop an inexpensive and high-precision touchless technology. A base substrate was coated with a luminescent material that emitted static-electricity-induced luminescence (SEL), and it was applied at high voltage. An inexpensive web camera was used to verify the relationship between the non-contact distance to a needle and the applied-voltage-triggered luminescence. The SEL was emitted at 20-200 mm from the luminescent device upon voltage application, and the web camera detected the SEL position with an accuracy of less than 1 mm. We used this developed touchless technology to demonstrate a highly accurate real-time detection of the position of a human finger based on SEL.
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COVID-19 , Luminescence , Humans , Static Electricity , TechnologyABSTRACT
The adsorption of chloroquine (CQ) and hydroxychloroquine (HCQ) on BC3nanosheets was evaluated and compared in gas and water media. The most desired complexes were obtained when the drug is parallel to the BC3surface, with an adsorption energy of −1.69 and −1.77 eV for CQ/bare and CQ/hydrogenated BC3complexes, respectively. The corresponding adsorption energies for HCQ/bare and HCQ/hydrogenated BC3nanosheets are −1.78 and −1.99 eV, respectively. It was found that the BC3nanosheets could be a suitable carrier of CQ and HCQ drugs, considering the amount of adsorption energy in the gas phase and water environment. The hydrogenated BC3nanosheet is a more prominent nanocarrier for CQ and HCQ than the bare BC3monolayer.
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Background: The dominance of SARS-CoV-2 Variants of Concern (VOC) and Interest (VOI) has challenged the efficacy of public health strategies to control the current pandemic. Astodrimer sodium is a broad-spectrum antiviral dendrimer that has been formulated as a topical nasal spray to help reduce exposure to infectious viral load in the nasal cavity. Astodrimer sodium showed antiviral and virucidal activity against early pandemic isolates of SARS-CoV-2 in vitro and after nasal administration in vivo. The current studies assessed the spectrum of activity of astodrimer sodium against emerging variants of SARS-CoV-2 and other pandemic viruses. Methods: Assays utilized hACE2+ and hTMPRSS2+ HEK-293T cells, Calu-3 and Vero E6 cells. Time of addition studies involved adding astodrimer sodium 1 hour prior to, at the time of, or 1-hour post-infection. Coronavirus spike receptor binding domain (RBD) or S1 binding studies were analysed by ELISA or confocal microscopy. Virucidal studies involved exposing 105 SARS-CoV-2 PFU to 10mg/mL astodrimer sodium for 0.5, 1, 5, 15 and 30 mins. Results: Astodrimer sodium demonstrated potent antiviral and virucidal activity against SARS-CoV-2 VOC α, β, δ and γ, and VOI κ in Vero E6 and Calu-3 cells. Astodrimer sodium reduced infectious viral load of all variants by >99.9% vs virus control. The pan-SARS-CoV-2 activity of astodrimer sodium occurred despite multiple mutations and deletions in the viral spike protein of each variant. The attachment of SARS-CoV-2 early pandemic virus isolates, Wuhan-Hu-1 and USA-WA-1/2020, and SARS-CoV-1 Spike binding to ACE2, as well as attachment of Middle Eastern respiratory syndrome (MERS) coronavirus spike protein to its cellular receptor, was inhibited by astodrimer sodium. Astodrimer sodium did not prevent attachment of the SARS-CoV-2 VOC α and β spike S1, or γ RBD spike protein, to the ACE2 receptor in vitro. Conclusion: Astodrimer sodium mimics negatively charged glycosaminoglycans and provides a potent antiviral and virucidal barrier to viral attachment and entry. The potent broad-spectrum anti-pandemic coronavirus and virucidal efficacy of astodrimer sodium against whole virus is likely due to blocking multiple electrostatic interactions of the spike protein that are not negated by minor or major changes to the isolated RBD of SARS-CoV-2 VOC α, β and γ alone. Astodrimer sodium has the potential to block the binding of pan-SARS-CoV-2, thus reducing the potential for the development of COVID-19.
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The coronavirus outbreak and its mutant variants have harmed the health of the human populace and imperiled the world economy. Several studies are initiated across the globe using clinical biomarkers from hematological, immunological, and biochemical experiments. In addition, analysis of protein interfaces provides an understanding of the functioning of the coronavirus target proteins. This study examines the interfaces of spike glycoproteins in terms of large (vdW dominant) and small (vdW subdominant) interfaces. We also calculated Gibbs free energy (?G), residue propensity and hot-spot prediction for these interfaces. Dataset consisting of 115 (large interface with vdW dominant) and 18 (small interface with vdW subdominant) were obtained from PDB. Results show that 86% of the total interfaces were vdW dominant, while the rest, 14%, were sub-dominant in vdW energy. Interestingly, on average, we found the Gibbs free energy (?G) of large and small interfaces to be -21 and -30 kcal/mol respectively. We also found the interfaces of large and small to be highly pronounced with polar residues followed by hydrophobic residues in case of large interfaces and charged residues in case of small interfaces. We found and report methionine residues to be absent at the small interfaces having subdominant vdW energy. We also observed the majority of the interfaces to be rich in hotspot residues. Thus, the information on heteromeric interactions of glycoproteins may help develop new and productive therapeutic drugs.
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Objective: The present study focused on binding mode of the N3 inhibitor and Ganomestenol with receptor SARS-CoV-2 Mpro protease. Methods: The structure of ligands N3 inhibitor and Ganomestenol were designed and 3-D coordinates were prepared using ACD/ChemSketch 8.0 freeware. Autodock4 software was used to study the orientation of the inhibitor or ligand in the active site of biological receptor SARS-CoV-2 Mpro (PDB ID: 6LU7). The Lamarckian genetic algorithm was applied to both ligand and protein for energy minimization using default parameters. The results were analyzed by Ligplot and Pymol software. Results: The compound Ganomestenol designed in in-silico for molecular docking with SARS-CoV-2 protease (Mpro). The in-silico results showed significant binding energy (−6.93 kcal/mol) by comparing with N3 inhibitor (−3.51 kcal/mol). Conclusion: The affinity of Ganomestenol is highly significant compared to N3 inhibitor and also showed efficacy of ligand toward protease under in-silico condition.
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Background: Within seconds of antigen-encounter, B-cell receptor (BCR) signaling induces dramatic changes of cell membrane lipid composition, including >40-fold increases of local PIP3-concentrations within lipid rafts. While several structural elements, including pleckstrin homology (PH) domains have been identified as PIP3-binding proteins, the underlying mechanisms that amplify BCR-signaling to assemble large signaling complexes within lipid rafts within 15 to 30 seconds, remained elusive. To understand the mechanistic and biophysical requirements for PIP3 accumulation during normal B-cell activation and acute oncogenic transformation, we identified PIP3-interacting proteins by cell-surface proteomic analyses. Results: In addition to proteins known to bind PIP3 with their PH-domains, we identified the short 133 aa protein IFITM3 (interferon-inducible transmembrane protein 3) as a top-ranking PIP3 scaffold. This was unexpected because IFITM3 was previously identified as endosomal protein that blocks viral infection by stiffening endosomal membranes to firmly contain viral cargo. Previous studies revealed that polymorphisms that lead to the expression of truncated IFITM3 are associated with increased susceptibility to viral infections, including SARS-CoV2. Among known cell membrane lipids, PIP3 has the highest negative charge. Instead of a PH-domain, IFITM3 laterally sequestered PIP3 through electrostatic interactions with two basic lysine residues (K83 and K104) located at the membrane-solution interface. Together with three other basic lysine and arginine residues K83 and K104 form a conserved intracellular loop (CIL), which enable IFITM3 to efficiently capture two PIP3 molecules. Bivalent PIP3-binding of the IFITM3-CIL enables a crosslinking mechanism that results in dramatic amplification of B-cell activation signals and clustering of large signaling complexes within lipid rafts. In normal resting B-cells, Ifitm3 was minimally expressed and mainly localized in endosomes. However, B-cell activation and oncogenic kinases induced phosphorylation at IFITM3-Y20, resulting in translocation of IFITM3 from endosomes and massive accumulation at the cell surface. Ifitm3ˉ /ˉ naïve B-cells developed at normal numbers, however, activation by antigen encounter was compromised. In Ifitm3ˉ /ˉ B-cells, lipid rafts were depleted of PIP3, resulting in defective expression of >60 lipid raft-associated surface receptors and impaired PI3K-signaling. Ifitm3ˉ /ˉ B-cells were unable to undergo affinity maturation and di not contribute to germinal center formation upon immunization. Analyses of gene expression and clinical outcome data from patients in six clinical cohorts for pediatric and adult B-ALL, mantle cell lymphoma, CLL and DLBCL, we consistently identified IFITM3 as a top-ranking predictor of poor clinical outcome. Inducible activation of BCR-ABL1 and NRAS G12D rapidly induced development of B-ALL but failed to transform and initiate B-ALL from Ifitm3ˉ /ˉ B-cell precursors. Conversely, the phospho-mimetic IFITM3-Y20E mutation, mimicking phosphorylation of the IFITM3 N-terminus at Y20 induced constitutive membrane localization of IFITM3, spontaneous aggregation of large oncogenic signaling complexes and readily initiated transformation in a genetic model of pre-malignant B-cells. Conclusions: We conclude that phosphorylation of IFITM3 upon B-cell activation induces a dynamic switch from antiviral effector functions in endosomes to oncogenic signal-amplification at the cell-surface. IFITM3-dependent amplification of PI3K-signaling is critical to enable rapid expansion of activated B-cells. In addition, multiple oncogenes depend on IFITM3 to assemble PIP3-dependent signaling complexes and amplify PI3K-signaling for malignant transformation and initiation of B-lymphoid leukemia and lymphoma. [Formula presented] Disclosures: Weinstock: SecuraBio: Consultancy;ASELL: Consultancy;Bantam: Consultancy;Abcuro: Research Funding;Verastem: Research Funding;Daiichi Sankyo: Consultancy, Research Funding;AstraZeneca: Consultanc ;Travera: Other: Founder/Equity;Ajax: Other: Founder/Equity.
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Recent development regarding mixture of H2 (concentration of ~66%) with O2 (concentration of ~34%) for medical purpose, such as treatment of coronavirus disease-19 (COVID-19) patients, is introduced. Furthermore, the design principles of a hydrogen inhaler which generates mixture of hydrogen (~66%) with oxygen (~34%) for medical purpose are proposed. With the installation of the liquid blocking module and flame arresters, the air pathway of the hydrogen inhaler is divided by multiple isolation zones to prevent any unexpected explosion propagating from one zone to the other. An integrated filtering/cycling module is utilized to purify the impurity, and cool down the temperature of the electrolytic module to reduce the risk of the explosion. Moreover, a nebulizer is provided to selectively atomize the water into vapor which is then mixed with the filtered hydrogen-oxygen mix gas, such that the static electricity of a substance hardly occurs to reduce the risk of the explosion. Furthermore, hydrogen concentration detector is installed to reduce the risk of hydrogen leakage. Result shows that the hydrogen inhaler implementing the aforesaid design rules could effectively inhibit the explosion, even ignition at the outset of the hydrogen inhaler which outputs hydrogen-oxygen gas (approximately 66% hydrogen: 34% oxygen).