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1.
J Phys Chem B ; 126(18): 3425-3430, 2022 May 12.
Article in English | MEDLINE | ID: covidwho-1815470

ABSTRACT

The SARS coronavirus 2 (SARS-CoV-2) spike protein is located at the outermost perimeter of the viral envelope and is the first component of the virus to make contact with surrounding interfaces. The stability of the spike protein when in contact with surfaces plays a deciding role for infection pathways and for the viability of the virus after surface contact. While cryo-EM structures of the spike protein have been solved with high resolution and structural studies in solution have provided information about the secondary and tertiary structures, only little is known about the folding when adsorbed to surfaces. We here report on the secondary structure and orientation of the S1 segment of the spike protein, which is often used as a model protein for in vitro studies of SARS-CoV-2, at the air-water interface using surface-sensitive vibrational sum-frequency generation (SFG) spectroscopy. The air-water interface plays an important role for SARS-CoV-2 when suspended in aerosol droplets, and it serves as a model system for hydrophobic surfaces in general. The SFG experiments show that the S1 segment of the spike protein remains folded at the air-water interface and predominantly binds in its monomeric state, while the combination of small-angle X-ray scattering and two-dimensional infrared spectroscopy measurements indicate that it forms hexamers with the same secondary structure in aqueous solution.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Spike Glycoprotein, Coronavirus/chemistry , Water/chemistry
2.
Chem Commun (Camb) ; 57(26): 3243-3246, 2021 Apr 04.
Article in English | MEDLINE | ID: covidwho-1747172

ABSTRACT

The hygroscopicity of respiratory aerosol determines their particle size distribution and regulates solute concentrations to which entrained microorganisms are exposed. Here, we report the hygroscopicity of simulated lung fluid (SLF) particles. While the response of aqueous particles follow simple mixing rules based on composition, we observe phase hysteresis with increasing and decreasing relative humidity (RH) and clear uptake of water prior to deliquescence. These results indicate that RH history may control the state of respiratory aerosol in the environment and influence the viability of microorganisms.


Subject(s)
Aerosols/analysis , Wettability , Body Fluids/chemistry , Humans , Humidity , Lung/chemistry , Particle Size , Water/chemistry
3.
J Photochem Photobiol B ; 229: 112415, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1712830

ABSTRACT

Noscapine (NSC) is a benzyl-isoquinoline alkaloid discovered in 1930 as an antitussive agent. Recently, NSC has also been reported to exhibit antitumor activity and, according to computational studies, it is able to attack the protease enzyme of Coronavirus (COVID-19) and thus could be used as antiviral for COVID-19 pandemic. Therefore, an increasing use of this drug could be envisaged in the coming years. NSC is readily metabolized with a half-life of 4.5 h giving rise to cotarnine, hydrocotarnine, and meconine, arising from the oxidative breaking of the CC bond between isoquinoline and phthalide moieties. Because of its potentially increasing use, high concentrations of NSC but also its metabolites will be delivered in the environment and potentially affect natural ecosystems. Thus, the aim of this work is to investigate the degradation of NSC in the presence of naturally occurring photocatalysts. As a matter of fact, the present contribution has demonstrated that NSC can be efficiently degraded in the presence of a derivative of the natural organic dye Riboflavin (RFTA) upon exposure to visible light. Indeed, a detailed study of the mechanism involved in the photodegradation revealed the similarities between the biomimetic and the photocatalyzed processes. In fact, the main photoproducts of NSC were identified as cotarnine and opianic acid based on a careful UPLC-MS2 analysis compared to the independently synthesized standards. The former is coincident with one of the main metabolites obtained in humans, whereas the latter is related to meconine, a second major metabolite of NSC. Photophysical experiments demonstrated that the observed oxidative cleavage is mediated mainly by singlet oxygen in a medium in which the lifetime of 1O2 is long enough, or by electron transfer to the triplet excited state of RFTA if the photodegradation occurs in aqueous media, where the 1O2 lifetime is very short.


Subject(s)
COVID-19 , Environmental Restoration and Remediation , Noscapine , Biomimetics , Chromatography, Liquid , Coloring Agents , Ecosystem , Humans , Light , Pandemics , Photolysis , Riboflavin/chemistry , Tandem Mass Spectrometry , Water/chemistry
4.
ACS Appl Mater Interfaces ; 14(7): 8718-8727, 2022 Feb 23.
Article in English | MEDLINE | ID: covidwho-1683917

ABSTRACT

Transparent antimicrobial coatings can maintain the aesthetic appeal of surfaces and the functionality of a touch-screen while adding the benefit of reducing disease transmission. We fabricated an antimicrobial coating of silver oxide particles in a silicate matrix on glass. The matrix was grown by a modified Stöber sol-gel process with vapor-phase water and ammonia. A coating on glass with 2.4 mg of Ag2O per mm2 caused a reduction of 99.3% of SARS-CoV-2 and >99.5% of Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus compared to the uncoated glass after 1 h. We envisage that screen protectors with transparent antimicrobial coatings will find particular application to communal touch-screens, such as in supermarkets and other check-out or check-in facilities where a number of individuals utilize the same touch-screen in a short interval.


Subject(s)
Anti-Infective Agents/chemistry , Bacterial Infections/prevention & control , COVID-19/prevention & control , Oxides/chemistry , Silver Compounds/chemistry , Ammonia/chemistry , Anti-Infective Agents/pharmacology , Bacterial Infections/microbiology , COVID-19/virology , Glass/chemistry , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Oxides/pharmacology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/pathogenicity , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Silicates/chemistry , Silver Compounds/pharmacology , Water/chemistry
5.
Molecules ; 27(2)2022 Jan 16.
Article in English | MEDLINE | ID: covidwho-1628349

ABSTRACT

Hendra virus (HeV) belongs to the paramyxoviridae family of viruses which is associated with the respiratory distress, neurological illness, and potential fatality of the affected individuals. So far, no competitive approved therapeutic substance is available for HeV. For that reason, the current research work was conducted to propose some novel compounds, by adopting a Computer Aided Drug Discovery approach, which could be used to combat HeV. The G attachment Glycoprotein (Ggp) of HeV was selected to achieve the primary objective of this study, as this protein makes the entry of HeV possible in the host cells. Briefly, a library of 6000 antiviral compounds was screened for potential drug-like properties, followed by the molecular docking of short-listed compounds with the Protein Data Bank (PDB) structure of Ggp. Docked complexes of top two hits, having maximum binding affinities with the active sites of Ggp, were further considered for molecular dynamic simulations of 200 ns to elucidate the results of molecular docking analysis. MD simulations and Molecular Mechanics Energies combined with the Generalized Born and Surface Area (MMGBSA) or Poisson-Boltzmann and Surface Area (MMPBSA) revealed that both docked complexes are stable in nature. Furthermore, the same methodology was used between lead compounds and HeV Ggp in complex with its functional receptor in human, Ephrin-B2. Surprisingly, no major differences were found in the results, which demonstrates that our identified compounds can also perform their action even when the Ggp is attached to the Ephrin-B2 ligand. Therefore, in light of all of these results, we strongly suggest that compounds (S)-5-(benzylcarbamoyl)-1-(2-(4-methyl-2-phenylpiperazin-1-yl)-2-oxoethyl)-6-oxo-3,6-dihydropyridin-1-ium-3-ide and 5-(cyclohexylcarbamoyl)-1-(2-((2-(3-fluorophenyl)-2-methylpropyl)amino)-2-oxoethyl)-6-oxo-3,6-dihydropyridin-1-ium-3-ide could be considered as potential therapeutic agents against HeV; however, further in vitro and in vivo experiments are required to validate this study.


Subject(s)
Antiviral Agents/chemistry , Computational Chemistry/methods , Viral Fusion Proteins/chemistry , Antiviral Agents/metabolism , Ephrin-B2/chemistry , Ephrin-B2/metabolism , Hendra Virus/drug effects , Humans , Hydrogen Bonding , Molecular Docking Simulation , Molecular Dynamics Simulation , Protein Binding , Receptors, Virus/chemistry , Receptors, Virus/metabolism , Small Molecule Libraries , Viral Fusion Proteins/antagonists & inhibitors , Viral Fusion Proteins/metabolism , Water/chemistry
6.
Int J Cosmet Sci ; 43(6): 748-763, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1506242

ABSTRACT

OBJECTIVE: The main objective of this paper is to analyse and attempt to understand the nature of rheological changes observed and the dynamics of Carbopol NF 980 hydroalcoholic gels neutralized specifically by triethanol amine (TEA), both as a function of time and alcohol type to probe time stabilities and ageing effects in such carbopol gel systems. The rheological changes and dynamics of 3 carbopol gel systems were observed; the gels included a water-based, ethanol-based, and isopropyl alcohol-based gel. It is hoped that this study shall shed light on the dynamical nature and the microstructural evolution of such networked gel systems, which were maintained under closed isothermal conditions and left completely unperturbed. The experimental results can provide the information necessary to understand and proposes plausible mechanisms guiding this dynamical behaviour in hydroalcoholic carbopol gels. METHODS: A TA instrument mechanical rheometer was used to measure the viscosity and storage and loss modulus, and a pH meter was utilized to determine the changes in each sample over the period. RESULTS: Studying the differences in the gel structures upon initial preparation illustrated that the ethanol and isopropyl alcohol (IPA) gels differed from the water-based gel in terms of viscosity, G', and G″, with the IPA gel displaying the lowest viscosity and moduli values across all shear rates. All the three gel systems exhibited strong shear thinning characteristics and were reminiscent of yield stress type found in colloidal gels. The water-based gel compared to the hydroalcoholic gels was strongly G' dominated, with the magnitude of the difference between G' and G″ observed to be much higher. This reflects that initial formation of the water-based gel structure possesses a much more rigid structure with a high elastic modulus component dominating. This also suggests that the water-based gel structure displayed stronger interactions between the carbopol particles when compared to those of the hydroalcoholic gels. Over the 30-day period, it was observed that the ethanol and water-based gels did not reveal any appreciable viscosity changes, with only an approximate 12% and 7% change from day 1 to 30, respectively. It was observed that the IPA systems' viscosity drastically increased over the period, with an approximately 77% change from day 1 to 30. The water and ethanol-based gels also exhibited very similar rheological behaviour over the entire time period with G' dominating G″. The G″ values of the water and ethanol-based gels decreased slightly at the end of day 30 by 10% and 16%, respectively, while the G' values for each sample remained essentially unchanged, increasing only 0.06% for the water-based gel, and increasing 1.4% for the ethanol-based gel. This further confirms the relatively stable gel structures attained. For the isopropyl gel system, the storage modulus of the system exhibited an average percent increase of approximately 16% from day 1 to day 30, but interestingly the loss modulus varied the least amongst all the gel systems, with only a 3% increase. The increase in G' reflects upon the evolution of a more rigid structure by day 30 for the IPA gel. This observation is clearly consistent with the corresponding increase in viscosity observed in the IPA gel. None of the gels tested displayed a consistent pH over the period. The pH of the hydroalcoholic gels was higher than that of the water-based gel for a majority of the period. The greatest fluctuations in pH were observed for the water and IPA gels, even though the water-based gel had one of the most stable rheological profiles out of the samples tested. The water, ethanol, and IPA gels' pH increased approximately 25%, 6%, and 5%, respectively, from day 1 to day 30. CONCLUSION: The rheological and pH study of the 3 hand sanitizer systems over a 30-day period allowed for rational insights into the plausible reasons responsible for driving the observed rheological changes in these unperturbed systems. For the water-based gel, we hypothesize that the changes observed are due to physical ageing, where the gel structure has evolved over time to eventually progress towards a more stabilized framework structure. The pH of the gel upon formation was on the lower side. Such a lower pH influences the formation of a gel, which is comparatively less swollen and occupies a slightly lesser volume, and thereby points to a much less compacted gel network structure or alternatively, a more fluid structure. If the particles moved around more, the system was not initially in a state of low energy, causing increased particle movement, and in turn, physical ageing. This could be responsible for the development of a physically altered structure over time. The gel structure dynamically attempts to minimize its free energy by becoming more rigid, which has been observed as being manifested in the decrease of both the viscosity and the G″. For the hydroalcoholic gels, we conjecture that ageing observed was a result of chemical ageing, and the alcohol type employed in the preparation is primarily responsible for exhibiting this effect. The polarities of ethyl alcohol and isopropyl alcohol are key to the stabilization of such resultant network structures which get formed because of neutralization. It has been observed in previous studies that with decreasing polarity, there was an increase in the neutralization needed to obtain the development of a structure half as well developed as the final resultant structure. Isopropyl alcohol is a much less polar solvent compared to ethanol and water, and therefore required higher levels of TEA as the base to neutralize the system. We conjecture that the charged TEA cationic species had a greater propensity to get exchanged with bulk solution in the vicinity of the polymer into the bulk solution, and that the pH fluctuation observed indicated a kinetic exchange process over time, causing the viscosity and moduli profiles to increase along with the pH. At this time though, further investigations need to be carried out to truly understand the underlying instability, and thus dynamics for gel systems of this type.


OBJECTIF: L'objectif principal de cet article est d'analyser et de tenter de comprendre la nature des changements rhéologiques observés et la dynamique des gels hydroalcooliques Carbopol NF 980 neutralisés spécifiquement par l'amine triéthanol (TEA), à la fois en fonction du temps et du type d'alcool pour sonder les stabilités temporelles et les effets du vieillissement dans de tels systèmes de gel carbopol. Les changements rhéologiques et la dynamique de 3 systèmes de gel de carbopol ont été observés ; les gels comprenaient un gel à base d'eau, d'éthanol et d'alcool isopropylique. On espère que cette étude éclairera la nature dynamique et l'évolution microstructurale de ces systèmes de gel en réseau, qui ont été maintenus dans des conditions isothermes fermées et laissés complètement imperturbables. Les résultats expérimentaux peuvent fournir les informations nécessaires pour comprendre et proposer des mécanismes plausibles guidant ce comportement dynamique dans les gels hydroalcooliques de carbopol. MÉTHODE: Un rhéomètre TA mécanique a été utilisé pour mesurer la viscosité, le module de stockage et de perte, et un pH-mètre a été utilisé pour déterminer les changements dans chaque échantillon au cours de la période. RÉSULTATS: L'étude des différences dans les structures du gel lors de la préparation initiale a montré que les gels d'éthanol et d'alcool isopropylique (IPA) différaient du gel à base d'eau en termes de viscosité, G' et G'' le gel IPA affichant les valeurs de viscosité et de modules les plus faibles pour tous les taux de cisaillement. Les trois systèmes de gel présentaient de fortes caractéristiques d'amincissement par cisaillement et rappelaient le type de contrainte d'élasticité que l'on trouve dans les gels colloïdaux. Le gel à base d'eau par rapport aux gels hydroalcooliques était fortement dominé par G', l'ampleur de la différence entre G' et G'' présentant une importance beaucoup plus élevée. Cela reflète le fait que la formation initiale de la structure de gel à base d'eau possède une structure beaucoup plus rigide avec un composant de module élastique élevé dominant. Cela suggère également que la structure du gel à base d'eau présentait des interactions plus fortes entre les particules de carbopol par rapport à celles des gels hydroalcooliques. Au cours de la période de 30 jours, il a été observé que l'éthanol et les gels à base d'eau n'ont révélé aucun changement de viscosité appréciable, avec seulement un changement approximatif de 12% et 7% du jour 1 au jour 30, respectivement. Il a été observé que la viscosité des systèmes IPA a considérablement augmenté au cours de la période, avec un changement d'environ 77% du jour 1 au jour 30. Les gels à base d'eau et d'éthanol ont également montré un comportement rhéologique très similaire sur toute la période, G' dominant G''. Les valeurs G'' des gels à base d'eau et d'éthanol ont légèrement diminué à la fin de la journée 30 de 10% et 16%, respectivement, tandis que les valeurs G' pour chaque échantillon sont restées essentiellement inchangées, n'augmentant que de 0,06% pour le gel à base d'eau et augmentant de 1,4% pour le gel à base d'éthanol. Cela confirme en outre les structures de gel relativement stables atteintes. Pour le système de gel isopropylique, le module de stockage du système a montré une augmentation moyenne d'environ 16% du jour 1 au jour 30, mais il est intéressant de noter que le module de perte variait le moins parmi tous les systèmes de gel, avec seulement une augmentation de 3%. L'augmentation de G' reflète l'évolution d'une structure plus rigide au jour 30 pour le gel IPA. Cette observation est clairement cohérente avec l'augmentation correspondante de la viscosité observée dans le gel IPA. Aucun des gels testés n'a montré un pH constant sur la période. Le pH des gels hydroalcooliques était supérieur à celui du gel à base d'eau pendant la majeure partie de la période. Les plus grandes fluctuations de pH ont été observées pour les gels d'eau et d'IPA, même si le gel à base d'eau avait l'un des profils rhéologiques les plus stables parmi les échantillons testés. Le pH de l'eau, de l'éthanol et des gels IPA a augmenté d'environ 25%, 6% et 5%, respectivement, du jour 1 au jour 30. CONCLUSION: L'étude rhéologique et pH des 3 systèmes de désinfectant pour les mains sur une période de 30 jours a permis d'obtenir des informations rationnelles sur les raisons plausibles responsables des changements rhéologiques observés dans ces systèmes non perturbés. Pour le gel à base d'eau, nous émettons l'hypothèse que les changements observés sont dus au vieillissement physique, où la structure du gel a évolué au fil du temps pour éventuellement progresser vers une structure plus stabilisée. Le pH du gel lors de la formation était dans la partie inférieure. Un pH aussi bas influence la formation d'un gel, qui est comparativement moins gonflé et occupe un volume légèrement inférieur, et indique ainsi une structure de réseau de gel beaucoup moins compactée ou autrement dit, une structure plus fluide. Si les particules se déplaçaient davantage, le système n'était pas initialement dans un état de faible énergie, ce qui entraînait une augmentation du mouvement des particules et, à son tour, un vieillissement physique. Cela pourrait être responsable du développement d'une structure physiquement modifiée au fil du temps. La structure du gel tente dynamiquement de minimiser son énergie libre en devenant plus rigide, ce qui a été observé comme se manifestant par la diminution de la viscosité et du G'' Pour les gels hydroalcooliques, nous pensons que le vieillissement observé était le résultat d'un vieillissement chimique, et le type d'alcool utilisé dans la préparation est principalement responsable de cet effet. Les polarités de l'alcool éthylique et de l'alcool isopropylique sont essentielles à la stabilisation de ces structures de réseau résultantes qui se forment en raison de la neutralisation. Il a été observé dans des études antérieures qu'avec la diminution de la polarité, il y avait une augmentation de la neutralisation nécessaire pour obtenir le développement d'une structure à moitié aussi bien développée que la structure résultante finale. L'alcool isopropylique est un solvant beaucoup moins polaire que l'éthanol et l'eau, et nécessitait donc des niveaux plus élevés de TEA comme base pour neutraliser le système. Nous pensons que les espèces cationiques TEA chargées avaient une plus grande propension à être échangées avec une solution en vrac à proximité du polymère, dans la solution en vrac, et que la fluctuation du pH observée indiquait un processus d'échange cinétique au fil du temps, entraînant une augmentation des profils de viscosité et de modules avec le pH. À l'heure actuelle, cependant, des recherches supplémentaires doivent être menées pour vraiment comprendre l'instabilité sous-jacente, et donc la dynamique des systèmes de gel de ce type.


Subject(s)
2-Propanol/chemistry , Acrylic Resins/chemistry , Ethanol/chemistry , Hydrogels/chemistry , Rheology , Water/chemistry
7.
J Toxicol Environ Health B Crit Rev ; 24(7): 325-336, 2021 10 03.
Article in English | MEDLINE | ID: covidwho-1455046

ABSTRACT

Water-only or soap and water solutions are considered a gold standard for skin decontamination. However, there is lack of conclusive data regarding their efficacy. The aim of this study was to summarize in vivo animal model data on skin decontamination using water-only, and/or soap and water. Covidence, Embase, MEDLINE, PubMed, Web of Science, and Google Scholar were searched to identify relevant articles using water-only or soap and water decontamination methods in in vivo animals. Data extraction was completed from studies, representing three animal models, and 11 contaminants. Results demonstrated water-only decontamination solutions led to complete decontamination in 3.1% (n = 16/524) protocols, incomplete decontamination in 90.6% (n = 475/524) of protocols, and mortality in 6.3% (n = 33/524) of protocols. Soap and water decontamination solutions resulted in complete decontamination in 6.9% (n = 8/116) protocols, incomplete decontamination in 92.2% (n = 107/116) of protocols, and mortality in 6.9% (n = 8/116) of protocols. Although water only, or soap and water is considered a gold standard for skin decontamination, most papers investigated found that water only, and soap and water provided incomplete decontamination. Due to the insufficient data, and limitations that hinder the applicability of available data, evidence indicates that more contemporary studies investigating skin decontamination are needed, and compared to other model species, including humans, when practical.


Subject(s)
Decontamination/methods , Skin/metabolism , Soaps/chemistry , Animals , Humans , Models, Animal , Skin/chemistry , Species Specificity , Water/chemistry
8.
J Phys Chem Lett ; 12(26): 6218-6226, 2021 Jul 08.
Article in English | MEDLINE | ID: covidwho-1387122

ABSTRACT

Following our previous work ( Chem. Sci. 2021, 12, 4889-4907), we study the structural dynamics of the SARS-CoV-2 Main Protease dimerization interface (apo dimer) by means of microsecond adaptive sampling molecular dynamics simulations (50 µs) using the AMOEBA polarizable force field (PFF). This interface is structured by a complex H-bond network that is stable only at physiological pH. Structural correlations analysis between its residues and the catalytic site confirms the presence of a buried allosteric site. However, noticeable differences in allosteric connectivity are observed between PFFs and non-PFFs. Interfacial polarizable water molecules are shown to appear at the heart of this discrepancy because they are connected to the global interface H-bond network and able to adapt their dipole moment (and dynamics) to their diverse local physicochemical microenvironments. The water-interface many-body interactions appear to drive the interface volume fluctuations and to therefore mediate the allosteric interactions with the catalytic cavity.


Subject(s)
Molecular Dynamics Simulation , SARS-CoV-2/metabolism , Viral Matrix Proteins/chemistry , Water/chemistry , Allosteric Site , COVID-19/pathology , COVID-19/virology , Catalytic Domain , Dimerization , Humans , Hydrogen Bonding , Hydrogen-Ion Concentration , SARS-CoV-2/isolation & purification , Viral Matrix Proteins/metabolism
9.
J Am Chem Soc ; 143(33): 12930-12934, 2021 08 25.
Article in English | MEDLINE | ID: covidwho-1358340

ABSTRACT

The main protease from SARS-CoV-2 is a homodimer. Yet, a recent 0.1-ms-long molecular dynamics simulation performed by D. E. Shaw's research group shows that it readily undergoes a symmetry-breaking event on passing from the solid state to aqueous solution. As a result, the subunits present distinct conformations of the binding pocket. By analyzing this long simulation, we uncover a previously unrecognized role of water molecules in triggering the transition. Interestingly, each subunit presents a different collection of long-lived water molecules. Enhanced sampling simulations performed here, along with machine learning approaches, further establish that the transition to the asymmetric state is essentially irreversible.


Subject(s)
SARS-CoV-2/enzymology , Viral Matrix Proteins/chemistry , Water/chemistry , COVID-19/pathology , COVID-19/virology , Crystallography, X-Ray , Humans , Hydrogen Bonding , Molecular Dynamics Simulation , Protein Structure, Quaternary , Protein Subunits/chemistry , Protein Subunits/metabolism , SARS-CoV-2/isolation & purification , Viral Matrix Proteins/metabolism
10.
Int J Mol Sci ; 22(8)2021 Apr 14.
Article in English | MEDLINE | ID: covidwho-1299443

ABSTRACT

Photodegradation of the aqueous solutions of acetylsalicylic acid, in the absence (ASA) and the presence of excipients (ASE), is demonstrated by the photoluminescence (PL). A shift of the PL bands from 342 and 338 nm to 358 and 361-397 nm for ASA and ASE in solid state and as aqueous solutions was reported. By exposure of the solution of ASA 0.3 M to UV light, a decrease in the PL band intensity was highlighted. This behavior was revealed for ASA in the presence of phosphate buffer (PB) having the pH equal to 6.4, 7, and 8 or by the interaction with NaOH 0.3 M. A different behavior was reported in the case of ASE. In the presence of PB, an increase in the intensity of the PL band of ASE simultaneously with a change of the ratio between the intensities of the bands at 361-364 and 394-397 nm was highlighted. The differences between PL spectra of ASA and ASE have their origin in the presence of salicylic acid (SAL). The interaction of ASE with NaOH induces a shift of the PL band at 405-407 nm. Arguments for the reaction of ASA with NaOH are shown by Raman scattering and FTIR spectroscopy.


Subject(s)
Aspirin/chemistry , Photolysis/radiation effects , Solutions/radiation effects , Water/chemistry , Aspirin/radiation effects , Cadmium Compounds/chemistry , Luminescence , Quantum Dots/chemistry , Spectrum Analysis, Raman , Ultraviolet Rays/adverse effects
11.
PLoS One ; 16(1): e0244885, 2021.
Article in English | MEDLINE | ID: covidwho-1251754

ABSTRACT

Human influenza virus infections occur annually worldwide and are associated with high morbidity and mortality. Hence, development of novel anti-influenza drugs is urgently required. Rice Power® extract developed by the Yushin Brewer Co. Ltd. is a novel aqueous extract of rice obtained via saccharization and fermentation with various microorganisms, such as Aspergillus oryzae, yeast [such as Saccharomyces cerevisiae], and lactic acid bacteria, possessing various biological and pharmacological properties. In our previous experimental screening with thirty types of Rice Power® extracts, we observed that the 30th Rice Power® (Y30) extract promoted the survival of influenza A virus-infected Madin-Darby canine kidney (MDCK) cells. Therefore, to identify compounds for the development of novel anti-influenza drugs, we aimed to investigate whether the Y30 extract exhibits anti-influenza A virus activity. In the present study, we demonstrated that the Y30 extract strongly promoted the survival of influenza A H1N1 Puerto Rico 8/34 (A/PR/8/34), California 7/09, or H3N2 Aichi 2/68 (A/Aichi/2/68) viruses-infected MDCK cells and inhibited A/PR/8/34 or A/Aichi/2/68 viruses infection and growth in the co-treatment and pre-infection experiments. The pre-treatment of Y30 extract on MDCK cells did not induce anti-influenza activity in the cell. The Y30 extract did not significantly affect influenza A virus hemagglutination, and neuraminidase and RNA-dependent RNA polymerase activities. Interestingly, the electron microscopy experiment revealed that the Y30 extract disrupts the integrity of influenza A virus particles by permeabilizing the viral membrane envelope, suggesting that Y30 extract has a direct virucidal effect against influenza A virus. Furthermore, we observed that compared to the ethyl acetate (EtOAc) extract, the water extract of Y30 extract considerably promoted the survival of cells infected with A/PR/8/34 virus. These results indicated that more anti-influenza components were present in the water extract of Y30 extract than in the EtOAc extract. Our results highlight the potential of a rice extract fermented with A. oryzae and S. cerevisiae as an anti-influenza medicine and a drug source for the development of anti-influenza compounds.


Subject(s)
Aspergillus oryzae/metabolism , Influenza A virus/drug effects , Oryza/chemistry , Oryza/microbiology , Plant Extracts/pharmacology , Saccharomyces cerevisiae/metabolism , Water/chemistry , Acetates/chemistry , Animals , Antiviral Agents/pharmacology , Dogs , Fermentation , Influenza A virus/growth & development , Influenza A virus/physiology , Madin Darby Canine Kidney Cells , Microbial Viability/drug effects
12.
Future Med Chem ; 13(17): 1435-1450, 2021 09.
Article in English | MEDLINE | ID: covidwho-1282696

ABSTRACT

The COVID-19 outbreak has thrown the world into an unprecedented crisis. It has posed a challenge to scientists around the globe who are working tirelessly to combat this pandemic. We herein report a set of molecules that may serve as possible inhibitors of the SARS-CoV-2 main protease. To identify these molecules, we followed a combinatorial structure-based strategy, which includes high-throughput virtual screening, molecular docking and WaterMap calculations. The study was carried out using Protein Data Bank structures 5R82 and 6Y2G. DrugBank, Enamine, Natural product and Specs databases, along with a few known antiviral drugs, were used for the screening. WaterMap analysis aided in the recognition of high-potential molecules that can efficiently displace binding-site waters. This study may help the discovery and development of antiviral drugs against SARS-CoV-2.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Coronavirus 3C Proteases/chemistry , Protease Inhibitors/chemistry , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Antiviral Agents/pharmacokinetics , Antiviral Agents/therapeutic use , Binding Sites/drug effects , Catalysis , Computer Simulation , Databases, Factual , High-Throughput Screening Assays , Humans , Molecular Docking Simulation , Molecular Structure , Protease Inhibitors/pharmacokinetics , Thermodynamics , Water/chemistry
13.
Biomolecules ; 10(7)2020 07 09.
Article in English | MEDLINE | ID: covidwho-1249669

ABSTRACT

Agro-industrial waste is a largely untapped natural resource of bioactive compounds including carotenoids and pectin. However, conventional solvent extraction involves the excessive use of organic solvents, costly equipment, and tedious operation. These limitations of conventional extraction methods could be prospectively overcome by the carotenoid-pectin hydrocolloidal complexation. The complexation of lycopene and pectin was efficiently promoted in an aqueous environment, resulting in the colloidal complexes that can be subsequently recovered by sedimentation or centrifugation. In this study, the potential of carotenoid-pectin complexation on tomato pomace containing carotenoids and pectin was evaluated. Tomato pomace is a rich source of lycopene, ß-carotene as well as pectin, making it suitable as the raw material for the carotenoid extraction. The extraction of carotenoid and pectin from tomato pomace was optimized using response surface methodology. The maximum recovery was 9.43 mg carotenoid fractions/100 g tomato pomace, while the purity of carotenoid-rich fractions was 92%. The antioxidant capacity of carotenoids extracted from the complexation method was found to be higher than that from the solvent extraction method. Moreover, extraction yield and antioxidant capacity of carotenoid obtained from the carotenoid-pectin complexation were comparable to that from solvent extraction. The carotenoid-pectin complexation is a promising green approach to valorize agro by-products for the extraction of valuable carotenoids.


Subject(s)
Lycopene/isolation & purification , Lycopersicon esculentum/chemistry , beta Carotene/isolation & purification , Chemical Fractionation , Chromatography, High Pressure Liquid , Industrial Waste/analysis , Lycopene/chemistry , Pectins , Water/chemistry , beta Carotene/chemistry
14.
Proteins ; 89(10): 1289-1299, 2021 10.
Article in English | MEDLINE | ID: covidwho-1233229

ABSTRACT

A novel virus, severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19) worldwide appeared in 2019. Detailed scientific knowledge of the members of the Coronaviridae family, including the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is currently lacking. Structural studies of the MERS-CoV proteins in the current literature are extremely limited. We present here detailed characterization of the structural properties of MERS-CoV macro domain in aqueous solution. Additionally, we studied the impacts of chosen force field parameters and parallel tempering simulation techniques on the predicted structural properties of MERS-CoV macro domain in aqueous solution. For this purpose, we conducted extensive Hamiltonian-replica exchange molecular dynamics simulations and Temperature-replica exchange molecular dynamics simulations using the CHARMM36m and AMBER99SB parameters for the macro domain. This study shows that the predicted secondary structure properties including their propensities depend on the chosen simulation technique and force field parameter. We perform structural clustering based on the radius of gyration and end-to-end distance of MERS-CoV macro domain in aqueous solution. We also report and analyze the residue-level intrinsic disorder features, flexibility and secondary structure. Furthermore, we study the propensities of this macro domain for protein-protein interactions and for the RNA and DNA binding. Overall, results are in agreement with available nuclear magnetic resonance spectroscopy findings and present more detailed insights into the structural properties of MERS CoV macro domain in aqueous solution. All in all, we present the structural properties of the aqueous MERS-CoV macro domain using different parallel tempering simulation techniques, force field parameters and bioinformatics tools.


Subject(s)
Middle East Respiratory Syndrome Coronavirus/chemistry , Middle East Respiratory Syndrome Coronavirus/metabolism , Molecular Dynamics Simulation , Water/chemistry , Water/metabolism , Humans , Protein Domains/physiology , Protein Structure, Secondary , Solutions
15.
Int J Mol Sci ; 22(6)2021 Mar 11.
Article in English | MEDLINE | ID: covidwho-1143517

ABSTRACT

The interactions at the atomic level between small molecules and the main components of cellular plasma membranes are crucial for elucidating the mechanisms allowing for the entrance of such small species inside the cell. We have performed molecular dynamics and metadynamics simulations of tryptophan, serotonin, and melatonin at the interface of zwitterionic phospholipid bilayers. In this work, we will review recent computer simulation developments and report microscopic properties, such as the area per lipid and thickness of the membranes, atomic radial distribution functions, angular orientations, and free energy landscapes of small molecule binding to the membrane. Cholesterol affects the behaviour of the small molecules, which are mainly buried in the interfacial regions. We have observed a competition between the binding of small molecules to phospholipids and cholesterol through lipidic hydrogen-bonds. Free energy barriers that are associated to translational and orientational changes of melatonin have been found to be between 10-20 kJ/mol for distances of 1 nm between melatonin and the center of the membrane. Corresponding barriers for tryptophan and serotonin that are obtained from reversible work methods are of the order of 10 kJ/mol and reveal strong hydrogen bonding between such species and specific phospholipid sites. The diffusion of tryptophan and melatonin is of the order of 10-7 cm2/s for the cholesterol-free and cholesterol-rich setups.


Subject(s)
1,2-Dipalmitoylphosphatidylcholine/chemistry , Cholesterol/chemistry , Dimyristoylphosphatidylcholine/chemistry , Melatonin/chemistry , Serotonin/chemistry , Tryptophan/chemistry , 1,2-Dipalmitoylphosphatidylcholine/metabolism , Cholesterol/metabolism , Dimyristoylphosphatidylcholine/metabolism , Hydrogen Bonding , Lipid Bilayers/chemistry , Lipid Bilayers/metabolism , Melatonin/metabolism , Molecular Dynamics Simulation , Serotonin/metabolism , Solutions , Static Electricity , Thermodynamics , Tryptophan/metabolism , Water/chemistry
16.
Adv Colloid Interface Sci ; 290: 102400, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1116130

ABSTRACT

We review concepts involved in describing the chemodynamic features of nanoparticles and apply the framework to gain physicochemical insights into interactions between SARS-CoV-2 virions and airborne particulate matter (PM). Our analysis is highly pertinent given that the World Health Organisation acknowledges that SARS-CoV-2 may be transmitted by respiratory droplets, and the US Center for Disease Control and Prevention recognises that airborne transmission of SARS-CoV-2 can occur. In our theoretical treatment, the virion is assimilated to a core-shell nanoparticle, and contributions of various interaction energies to the virion-PM association (electrostatic, hydrophobic, London-van der Waals, etc.) are generically included. We review the limited available literature on the physicochemical features of the SARS-CoV-2 virion and identify knowledge gaps. Despite the lack of quantitative data, our conceptual framework qualitatively predicts that virion-PM entities are largely able to maintain equilibrium on the timescale of their diffusion towards the host cell surface. Comparison of the relevant mass transport coefficients reveals that virion biointernalization demand by alveolar host cells may be greater than the diffusive supply. Under such conditions both the free and PM-sorbed virions may contribute to the transmitted dose. This result points to the potential for PM to serve as a shuttle for delivery of virions to host cell targets. Thus, our critical review reveals that the chemodynamics of virion-PM interactions may play a crucial role in the transmission of COVID-19, and provides a sound basis for explaining reported correlations between episodes of air pollution and outbreaks of COVID-19.


Subject(s)
COVID-19/transmission , Epithelial Cells/virology , Particulate Matter/chemistry , SARS-CoV-2/chemistry , Virion/chemistry , Aerosols , Biomechanical Phenomena , COVID-19/virology , Diffusion , Humans , Hydrophobic and Hydrophilic Interactions , Models, Chemical , Nanoparticles/chemistry , Pulmonary Alveoli/virology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Static Electricity , Virion/metabolism , Virion/pathogenicity , Virus Internalization , Water/chemistry
17.
Biophys J ; 120(6): 1105-1119, 2021 03 16.
Article in English | MEDLINE | ID: covidwho-1103746

ABSTRACT

Cell penetration after recognition of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus by the ACE2 receptor and the fusion of its viral envelope membrane with cellular membranes are the early steps of infectivity. A region of the Spike protein of the virus, identified as the "fusion peptide" (FP), is liberated at its N-terminal site by a specific cleavage occurring in concert with the interaction of the receptor-binding domain of the Spike. Studies have shown that penetration is enhanced by the required binding of Ca2+ ions to the FPs of coronaviruses, but the mechanisms of membrane insertion and destabilization remain unclear. We have predicted the preferred positions of Ca2+ binding to the SARS-CoV-2-FP, the role of Ca2+ ions in mediating peptide-membrane interactions, the preferred mode of insertion of the Ca2+-bound SARS-CoV-2-FP, and consequent effects on the lipid bilayer from extensive atomistic molecular dynamics simulations and trajectory analyses. In a systematic sampling of the interactions of the Ca2+-bound peptide models with lipid membranes, SARS-CoV-2-FP penetrated the bilayer and disrupted its organization only in two modes involving different structural domains. In one, the hydrophobic residues F833/I834 from the middle region of the peptide are inserted. In the other, more prevalent mode, the penetration involves residues L822/F823 from the LLF motif, which is conserved in CoV-2-like viruses, and is achieved by the binding of Ca2+ ions to the D830/D839 and E819/D820 residue pairs. FP penetration is shown to modify the molecular organization in specific areas of the bilayer, and the extent of membrane binding of the SARS-CoV-2 FP is significantly reduced in the absence of Ca2+ ions. These findings provide novel mechanistic insights regarding the role of Ca2+ in mediating SARS-CoV-2 fusion and provide a detailed structural platform to aid the ongoing efforts in rational design of compounds to inhibit SARS-CoV-2 cell entry.


Subject(s)
Calcium/metabolism , Cell Membrane/metabolism , Recombinant Fusion Proteins/metabolism , SARS-CoV-2/metabolism , Amino Acid Sequence , Cell Membrane Permeability , Membrane Lipids/chemistry , Molecular Dynamics Simulation , Pressure , Probability , Protein Stability , Recombinant Fusion Proteins/chemistry , Water/chemistry
18.
Molecules ; 25(24)2020 Dec 11.
Article in English | MEDLINE | ID: covidwho-979528

ABSTRACT

We present a detailed computational study of the UV/Vis spectra of four relevant flavonoids in aqueous solution, namely luteolin, kaempferol, quercetin, and myricetin. The absorption spectra are simulated by exploiting a fully polarizable quantum mechanical (QM)/molecular mechanics (MM) model, based on the fluctuating charge (FQ) force field. Such a model is coupled with configurational sampling obtained by performing classical molecular dynamics (MD) simulations. The calculated QM/FQ spectra are compared with the experiments. We show that an accurate reproduction of the UV/Vis spectra of the selected flavonoids can be obtained by appropriately taking into account the role of configurational sampling, polarization, and hydrogen bonding interactions.


Subject(s)
Flavonoids/chemistry , Water/chemistry , Computer Simulation , Hydrogen Bonding , Molecular Conformation , Molecular Dynamics Simulation , Normal Distribution , Physical Phenomena , Quantum Theory , Spectrophotometry, Ultraviolet , Static Electricity , Ultraviolet Rays
19.
Nano Lett ; 21(4): 1576-1583, 2021 02 24.
Article in English | MEDLINE | ID: covidwho-960293

ABSTRACT

Recently, bioaerosols, including the 2019 novel coronavirus, pose a serious threat to global public health. Herein, we introduce a visible-light-activated (VLA) antimicrobial air filter functionalized with titanium dioxide (TiO2)-crystal violet (CV) nanocomposites facilitating abandoned visible light from sunlight or indoor lights. The TiO2-CV based VLA antimicrobial air filters exhibit a potent inactivation rate of ∼99.98% and filtration efficiency of ∼99.9% against various bioaerosols. Under visible-light, the CV is involved in overall inactivation by inducing reactive oxygen species production both directly (CV itself) and indirectly (in combination with TiO2). Moreover, the susceptibility of the CV to humidity was significantly improved by forming a hydrophobic molecular layer on the TiO2 surface, highlighting its potential applicability in real environments such as exhaled or humid air. We believe this work can open a new avenue for designing and realizing practical antimicrobial technology using ubiquitous visible-light energy against the threat of infectious bioaerosols.


Subject(s)
Air Microbiology , Anti-Infective Agents, Local/chemistry , Disinfection/methods , Gentian Violet/chemistry , Nanocomposites/chemistry , Titanium/chemistry , Anti-Infective Agents, Local/pharmacology , Bacteria/drug effects , Bacteria/radiation effects , Bacterial Infections/prevention & control , COVID-19/prevention & control , Disinfection/instrumentation , Filtration/instrumentation , Filtration/methods , Gentian Violet/pharmacology , Humans , Light , Nanocomposites/ultrastructure , Titanium/pharmacology , Water/chemistry
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