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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 244: 118825, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-32866803

RESUMO

Novel antiviral active molecule 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro- phenyl)acetamide has been synthesised and characterized by FT-IR and FT-Raman spectra. The equilibrium geometry, natural bond orbital calculations and vibrational assignments have been carried out using density functional B3LYP method with the 6-311G++(d,p) basis set. The complete vibrational assignments for all the vibrational modes have been supported by normal coordinate analysis, force constants and potential energy distributions. A detailed analysis of the intermolecular interactions has been performed based on the Hirshfeld surfaces. Drug likeness has been carried out based on Lipinski's rule and the absorption, distribution, metabolism, excretion and toxicity of the title molecule has been calculated. Antiviral potency of 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro-phenyl) acetamide has been investigated by docking against SARS-CoV-2 protein. The optimized geometry shows near-planarity between the phenyl ring and the pyrimidine ring. Differences in the geometries due to the substitution of the most electronegative fluorine atom and intermolecular contacts due to amino pyrimidine were analyzed. NBO analysis reveals the formation of two strong stable hydrogen bonded N-H···N intermolecular interactions and weak intramolecular interactions C-H···O and N-H···O. The Hirshfeld surfaces and consequently the 2D-fingerprint confirm the nature of intermolecular interactions and their quantitative contributions towards the crystal packing. The red shift in N-H stretching frequency exposed from IR substantiate the formation of N-H···N intermolecular hydrogen bond. Drug likeness and absorption, distribution, metabolism, excretion and toxicity properties analysis gives an idea about the pharmacokinetic properties of the title molecule. The binding energy -8.7 kcal/mol of the nonbonding interaction present a clear view that 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro- phenyl) acetamide can irreversibly interact with SARS-CoV-2 protease.


Assuntos
Antivirais/química , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pandemias , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteases/química , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/farmacocinética , Betacoronavirus/enzimologia , Cristalografia por Raios X , Cisteína Endopeptidases , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Dinâmica não Linear , Inibidores de Proteases/farmacocinética , Conformação Proteica , Teoria Quântica , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Termodinâmica , Vibração
2.
Nat Commun ; 11(1): 4923, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004824

RESUMO

A goal of biology is to predict how mutations combine to alter phenotypes, fitness and disease. It is often assumed that mutations combine additively or with interactions that can be predicted. Here, we show using simulations that, even for the simple example of the lambda phage transcription factor CI repressing a gene, this assumption is incorrect and that perfect measurements of the effects of mutations on a trait and mechanistic understanding can be insufficient to predict what happens when two mutations are combined. This apparent paradox arises because mutations can have different biophysical effects to cause the same change in a phenotype and the outcome in a double mutant depends upon what these hidden biophysical changes actually are. Pleiotropy and non-monotonic functions further confound prediction of how mutations interact. Accurate prediction of phenotypes and disease will sometimes not be possible unless these biophysical ambiguities can be resolved using additional measurements.


Assuntos
Fenômenos Biofísicos/genética , Estudos de Associação Genética/métodos , Modelos Genéticos , Termodinâmica , Bacteriófago lambda/genética , Regulação Viral da Expressão Gênica , Mutação , Fenótipo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteínas Virais Reguladoras e Acessórias/genética , Proteínas Virais Reguladoras e Acessórias/metabolismo
3.
Artigo em Inglês | MEDLINE | ID: mdl-33017917

RESUMO

Prolonged measurement of total body volume variations (deltaVb) with whole-body, flow-based plethysmography (WBP) results in a drift of the signal due to changes in temperature and humidity inside the plethysmograph and to numerical integration of the flow to obtain deltaVb. This drift has been previously corrected with the application of a wavelet- based filter using visual inspection of the signal to select the optimal filter level (Uva et al. Front. Physiol. 6:411, 2016), thus introducing potential operator bias. To exclude the latter we compared this approach with a newly developed automatic method based on (1) correction for actual changes in temperature and humidity inside the plethysmograph (algorithm TH) and (2) automatic selection of the wavelet filter level based on comparison between deltaVb and intra-thoracic and abdominal pressure variations measured simultaneously (algorithm WAV). The Pearson's correlation coefficient between deltaVb and the changes in volume of the chest wall (deltaVcw) simultaneously obtained by optoelectronic plethysmography (OEP) was calculated after correction of deltaVb with TH and WAV applied separately, TH and WAV applied consecutively (TH+WAV), manual selection of a wavelet filter based on visual inspection (MAN) or no correction (CTRL). The correlation between deltaVb and deltaVcw increased marginally with WAV, TH+WAV and MAN compared to CTRL (P <; 0.01). Conversely, TH alone yielded a lower correlation (P <; 0.01). It follows that while the automated wavelet filter level selection method (WAV) represents an effective, operator-independent method for the correction of deltaVb, whether or not it is combined with specific correction for changes in thermodynamic conditions inside the plethysmograph, the manual method (MAN) yields satisfactory results without the constraints of intra-thoracic and abdominal pressure measurement.


Assuntos
Algoritmos , Pletismografia , Pletismografia Total , Temperatura , Termodinâmica
4.
Water Sci Technol ; 82(4): 651-662, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32970618

RESUMO

The adsorption isotherms of Reactive Red 120 (RR-120) on Brazilian pine-fruit shell activated carbon, at six temperatures (298, 303, 308, 313, 318 and 323 K) and pH = 6, were determined and interpreted using a double layer model with one energy. A statistical physics treatment established the formulation of this model. Steric and energetic parameters related to the adsorption process, such as the number of adsorbed molecules per site, the receptor sites density and the concentration at half-saturation, have been considered. Thermodynamic potential functions such as entropy, internal energy and Gibbs free enthalpy are analyzed, and the choice of the models is based on assumptions in correlation with experimental conditions. By numerical fitting, the investigated parameters were deduced. The theoretical expressions provide a good understanding and interpretation of the adsorption isotherms at the microscopic level. We believe that our work contributes to new theoretical insights on the dye adsorption in order to know the physical nature of the adsorption process.


Assuntos
Carvão Vegetal , Triazinas , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Termodinâmica
5.
Water Sci Technol ; 82(4): 673-682, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32970620

RESUMO

Loess is a typical natural mineral particle distributed widely around the world, and it is inexpensive, readily accessible, and harmless to the environment. In this study, loess was modified by surface grafting copolymerization of functional monomers, such as acrylic acid, N-vinyl pyrrolidone, and N,N-methylenebisacrylamide as a cross-linking agent, which afforded a novel loess-based grafting copolymer (LC-PAVP). After being characterized by scanning electron microscopy, thermal gravimetric analysis and Fourier-transform infrared spectroscopy, its adsorption capacity and mechanism of removing lead ions (Pb2+) were investigated. With the study of the optimal experimental conditions, it was demonstrated that the removal rate of Pb2+ by LC-PAVP can reach up to 99.49% in 60 min at room temperature. It was also found that the kinetic characteristics of the adsorption capacity due to the pseudo-second-order kinetic model and the thermodynamics conformed well with the Freundlich model. In summary, as a lost-cost and eco-friendly loess-based adsorbent, LC-PAVP is a good potential material for wastewater treatment.


Assuntos
Acrilatos , Poluentes Químicos da Água/análise , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Polímeros , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Águas Residuárias
6.
Water Sci Technol ; 82(4): 715-731, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32970624

RESUMO

In the present work, native chitosan (Ch) along with its chemically and physico-chemically modified versions, namely sulphate cross-linked chitosan (SCC) and sulphate cross-linked chitosan-bentonite composite (SCC-B), were employed as potential adsorbents for the removal of an anionic dye, Alizarin Red S (ARS) from aqueous solutions. All three adsorbents were extensively characterized using techniques such as Fourier-transform infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray, X-ray diffraction, Brunauer-Emmett-Teller analysis, thermogravimetric-differential thermal analysis, and pH point of zero charge. Various parameters were optimized, including pH of dye solution, contact time, adsorbent dose, initial adsorbate concentration and temperature of adsorption. Four adsorption isotherm models were studied and it was found that the Freundlich model was best-fit for all three systems. Maximum adsorption capacities towards adsorption of ARS were found to be 42.48, 109.12 and 131.58 mg g-1 for Ch, SCC and SCC-B, respectively. Kinetics of adsorption was examined by employing three well-known models in order to deduce the mechanism of adsorption. Thermodynamic studies show that the process is spontaneous and exothermic for all adsorbents employed. Furthermore, it was observed that for large sample volumes, the column adsorption method was more effective compared to the batch method.


Assuntos
Quitosana , Poluentes Químicos da Água , Adsorção , Antraquinonas , Humanos , Concentração de Íons de Hidrogênio , Cinética , Deficiência Energética Relativa no Esporte , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica
7.
Water Sci Technol ; 82(4): 747-758, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32970626

RESUMO

The eco-friendly and non-toxic natural organic substance, insolubilized humic acid (IHA), was used to remove Mn(II) from aqueous solutions. The adsorption characteristics were studied through a series of static adsorption tests. The results show that conditions such as the dose, the pH of the solution and the initial concentration of Mn(II) all affect removal efficiency, and the optimal pH value was 5.5. The sorption process for Mn(II) on IHA conforms to the pseudo-second-order adsorption kinetic model and intra-particle diffusion is not the only factor affecting the adsorption rate. Both Langmuir and Freundlich models can describe this adsorption behavior, and the experimental maximum adsorption capacity of IHA was 52.87 mg/g under optimal conditions. The thermodynamic analysis of adsorption shows that the adsorption process is a non-spontaneous endothermic physical reaction. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) were used to characterize the samples, it was found that as IHA successfully adsorbed Mn(II), the surface morphology of IHA changed after the adsorption reaction. The adsorption mechanism for Mn(II) on IHA is to provide electron pairs for carboxyl, phenolic hydroxyl and other functional groups to form stable complexes with Mn(II).


Assuntos
Poluentes Químicos da Água/análise , Adsorção , Substâncias Húmicas , Concentração de Íons de Hidrogênio , Cinética , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica
8.
Water Sci Technol ; 82(3): 427-439, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32960789

RESUMO

The occurrence of organic micropollutants such as pharmaceutical drugs and hormones in the environment reflects the inefficiency of traditional wastewater treatment technologies. Biosorption is a promising alternative from a technical-economic point of view, so understanding the mechanisms of adsorption in new biosorbents is vital for application and process optimization. Within this context, this study aims to evaluate the mechanisms of adsorption and removal of synthetic and natural hormones by Pinus elliottii bark biosorbent (PS) compared to commercial granular activated carbon (GAC) through kinetic models, isotherm models, and thermodynamic models. The adsorbents were also characterized by morphology, chemical composition, functional groups, and point of zero charge. Characterization of the adsorbents highlights the heterogeneous and fibrous morphology and broader range of functional groups found for PS. Kinetic adjustments showed high accuracy for pseudo-second-order, Elovich, and intraparticle diffusion models, presenting multilinearity and evidencing multi-stage adsorption. The isotherms for PS followed high-affinity models, predominantly chemisorption, while those for GAC followed the Langmuir model, where physisorption predominates. These mechanisms were confirmed by thermodynamic models, which also indicated a higher dependence on temperature in the adsorption process. In the fortified water removal test, PS showed removal values higher than GAC, highlighting the advantages of this adsorbent.


Assuntos
Poluentes Químicos da Água/análise , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Lignina , Termodinâmica
9.
Water Sci Technol ; 82(3): 468-480, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32960792

RESUMO

In this work, a biosorbent was prepared by the ultrasound-acid treatment of Merremia vitifolia plant and tested for the removal of 2,4-dichlorophenoxyacetic acid (2,4-D), a phenoxy herbicide. Optimal values of five batch biosorption parameters namely stirring speed, contact time, biosorbent dosage, initial pH and initial adsorbate concentration were experimentally obtained in sequential manner for an enhanced biosorption capacity. The kinetics of the biosorption of 2,4-D were best described by the pseudo first order kinetic model (R2 = 0.99) and the biosorption equilibrium data were successfully fitted to the Langmuir adsorption isotherm (R2 = 0.99) with a maximum biosorption capacity of 66.93 mg g-1. The mechanism of biosorption was investigated using two intraparticle diffusion models (Weber and Boyd), Dubinin-Radushkevich isotherm model and electrostatic interactions. The presence of intraparticle and film diffusion limitations for the biosorption was confirmed along with the physical and chemical nature of the biosorption. The thermodynamic parameters of the biosorption were calculated using the equilibrium data obtained at four different temperatures. The entropy change for biosorption was found to be negative indicating the decreased randomness at the interface. Desorption studies were carried out using different solvents and the percentages of desorption were compared.


Assuntos
Convolvulaceae , Herbicidas , Poluentes Químicos da Água , Ácido 2,4-Diclorofenoxiacético , Adsorção , Biomassa , Concentração de Íons de Hidrogênio , Cinética , Termodinâmica
10.
Water Sci Technol ; 82(1): 157-169, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32910800

RESUMO

The dynamic characteristics of N2O emissions and nitrogen transformation in a sequencing batch biofilm reactor (SBBR) using the completely autotrophic nitrogen removal over nitrite (CANON) process coupled with denitrification were investigated via 15N isotope tracing and thermodynamic analysis. The results indicate that the Gibbs free energy (ΔG) values of N2O production by the nitrifier denitrification and heterotrophic denitrification reactions were greater than that of NH2OH oxidation, indicating that N2O was easier to produce via either nitrifier and heterotrophic denitrification than via NH2OH oxidation. Ammonia-oxidizing bacteria (AOB) denitrification exhibited a higher fs0 (the fraction of electron-donor electrons utilized for cell synthesis) than NH2OH oxidation. Therefore, AOB preferred the denitrification pathway because of its growth advantage when N2O was produced by the AOB. The N2O emissions by hydroxylamine oxidation, AOB denitrification and heterotrophic denitrification in the SBBRs using different C/N ratios account for 5.4-7.6%, 45.2-60.8% and 33.8-47.2% of the N2O produced, respectively. The total N2O emission with C/N ratios of 0, 0.67 and 1 was 228.04, 205.57 and 190.4 µg N2O-N·g-1VSS, respectively. The certain carbon sources aid in the reduction of N2O emissions in the process.


Assuntos
Nitritos , Óxido Nitroso , Desnitrificação , Nitrogênio , Termodinâmica
11.
PLoS Comput Biol ; 16(9): e1008132, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32877399

RESUMO

Tubulin dimers associate longitudinally and laterally to form metastable microtubules (MTs). MT disassembly is preceded by subtle structural changes in tubulin fueled by GTP hydrolysis. These changes render the MT lattice unstable, but it is unclear exactly how they affect lattice energetics and strain. We performed long-time atomistic simulations to interrogate the impacts of GTP hydrolysis on tubulin lattice conformation, lateral inter-dimer interactions, and (non-)local lateral coordination of dimer motions. The simulations suggest that most of the hydrolysis energy is stored in the lattice in the form of longitudinal strain. While not significantly affecting lateral bond stability, the stored elastic energy results in more strongly confined and correlated dynamics of GDP-tubulins, thereby entropically destabilizing the MT lattice.


Assuntos
Microtúbulos , Tubulina (Proteína) , Guanosina Trifosfato/química , Guanosina Trifosfato/metabolismo , Hidrólise , Microtúbulos/química , Microtúbulos/metabolismo , Microtúbulos/fisiologia , Simulação de Dinâmica Molecular , Conformação Proteica , Termodinâmica , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/fisiologia
12.
Nat Commun ; 11(1): 4851, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978386

RESUMO

Cell factories converting bio-based precursors to chemicals present an attractive avenue to a sustainable economy, yet screening of genetically diverse strain libraries to identify the best-performing whole-cell biocatalysts is a low-throughput endeavor. For this reason, transcriptional biosensors attract attention as they allow the screening of vast libraries when used in combination with fluorescence-activated cell sorting (FACS). However, broad ligand specificity of transcriptional regulators (TRs) often prohibits the development of such ultra-high-throughput screens. Here, we solve the structure of the TR LysG of Corynebacterium glutamicum, which detects all three basic amino acids. Based on this information, we follow a semi-rational engineering approach using a FACS-based screening/counterscreening strategy to generate an L-lysine insensitive LysG-based biosensor. This biosensor can be used to isolate L-histidine-producing strains by FACS, showing that TR engineering towards a more focused ligand spectrum can expand the scope of application of such metabolite sensors.


Assuntos
Sistemas de Transporte de Aminoácidos Básicos/química , Proteínas de Bactérias/química , Técnicas Biossensoriais/métodos , Ligantes , Engenharia Metabólica/métodos , Sistemas de Transporte de Aminoácidos Básicos/metabolismo , Proteínas de Bactérias/metabolismo , Corynebacterium glutamicum/metabolismo , Cristalografia , Citometria de Fluxo/métodos , Ensaios de Triagem em Larga Escala/métodos , Lisina/metabolismo , Técnicas Analíticas Microfluídicas , Modelos Moleculares , Conformação Proteica , Domínios Proteicos , Termodinâmica
13.
Molecules ; 25(17)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867349

RESUMO

Three types of new coronaviruses (CoVs) have been identified recently as the causative viruses for the severe pneumonia-like respiratory illnesses, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and corona-virus disease 2019 (COVID-19). Neither therapeutic agents nor vaccines have been developed to date, which is a major drawback in controlling the present global pandemic of COVID-19 caused by SARS coronavirus 2 (SARS-CoV-2) and has resulted in more than 20,439,814 cases and 744,385 deaths. Each of the 3C-like (3CL) proteases of the three CoVs is essential for the proliferation of the CoVs, and an inhibitor of the 3CL protease (3CLpro) is thought to be an ideal therapeutic agent against SARS, MERS, or COVID-19. Among these, SARS-CoV is the first corona-virus isolated and has been studied in detail since the first pandemic in 2003. This article briefly reviews a series of studies on SARS-CoV, focusing on the development of inhibitors for the SARS-CoV 3CLpro based on molecular interactions with the 3CL protease. Our recent approach, based on the structure-based rational design of a novel scaffold for SARS-CoV 3CLpro inhibitor, is also included. The achievements summarized in this short review would be useful for the design of a variety of novel inhibitors for corona-viruses, including SARS-CoV-2.


Assuntos
Antivirais/química , Betacoronavirus/química , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Inibidores de Proteases/química , Vírus da SARS/patogenicidade , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/classificação , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/enzimologia , Domínio Catalítico , Infecções por Coronavirus/tratamento farmacológico , Cristalografia por Raios X , Cisteína Endopeptidases/química , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Humanos , Cinética , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteases/classificação , Inibidores de Proteases/uso terapêutico , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Vírus da SARS/genética , Vírus da SARS/metabolismo , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Especificidade por Substrato , Termodinâmica , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
14.
Molecules ; 25(17)2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32872217

RESUMO

A pandemic caused by the novel coronavirus (SARS-CoV-2 or COVID-19) began in December 2019 in Wuhan, China, and the number of newly reported cases continues to increase. More than 19.7 million cases have been reported globally and about 728,000 have died as of this writing (10 August 2020). Recently, it has been confirmed that the SARS-CoV-2 main protease (Mpro) enzyme is responsible not only for viral reproduction but also impedes host immune responses. The Mpro provides a highly favorable pharmacological target for the discovery and design of inhibitors. Currently, no specific therapies are available, and investigations into the treatment of COVID-19 are lacking. Therefore, herein, we analyzed the bioactive phytocompounds isolated by gas chromatography-mass spectroscopy (GC-MS) from Tinospora crispa as potential COVID-19 Mpro inhibitors, using molecular docking study. Our analyses unveiled that the top nine hits might serve as potential anti-SARS-CoV-2 lead molecules, with three of them exerting biological activity and warranting further optimization and drug development to combat COVID-19.


Assuntos
Antivirais/química , Betacoronavirus/química , Compostos Fitoquímicos/química , Inibidores de Proteases/química , Tinospora/química , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/classificação , Antivirais/isolamento & purificação , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/enzimologia , Domínio Catalítico , Infecções por Coronavirus/tratamento farmacológico , Cisteína Endopeptidases/química , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Descoberta de Drogas , Cromatografia Gasosa-Espectrometria de Massas , Expressão Gênica , Humanos , Cinética , Simulação de Acoplamento Molecular , Pandemias , Compostos Fitoquímicos/classificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteases/classificação , Inibidores de Proteases/isolamento & purificação , Inibidores de Proteases/farmacologia , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , Especificidade por Substrato , Termodinâmica , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
15.
Chemosphere ; 258: 127279, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947678

RESUMO

Adsorption is widely applied separation process, especially in environmental remediation, due to its low cost and high efficiency. Adsorption isotherm models can provide mechanism information of the adsorption process, which is important for the design of adsorption system. However, the classification, physical meaning, application and solving method of the isotherms have not been systematical analyzed and summarized. In this paper, the adsorption isotherms were classified into adsorption empirical isotherms, isotherms based on Polanyi's theory, chemical adsorption isotherms, physical adsorption isotherms, and the ion exchange model. The derivation and physical meaning of the isotherm models were discussed in detail. In addition, the application of the isotherm models were analyzed and summarized based on over 200 adsorption equilibrium data in literature. The statistical parameters for evaluating the fitness of the models were also discussed. Finally, a user interface (UI) was developed based on Excel software for solving the isotherm models, which was provided in supplemental material and can be easily used to model the adsorption equilibrium data. This paper will provide theoretical basis and guiding methodology for the selection and use of the adsorption isotherms.


Assuntos
Adsorção , Modelos Químicos , Software , Termodinâmica
16.
Molecules ; 25(17)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: covidwho-737517

RESUMO

Three types of new coronaviruses (CoVs) have been identified recently as the causative viruses for the severe pneumonia-like respiratory illnesses, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and corona-virus disease 2019 (COVID-19). Neither therapeutic agents nor vaccines have been developed to date, which is a major drawback in controlling the present global pandemic of COVID-19 caused by SARS coronavirus 2 (SARS-CoV-2) and has resulted in more than 20,439,814 cases and 744,385 deaths. Each of the 3C-like (3CL) proteases of the three CoVs is essential for the proliferation of the CoVs, and an inhibitor of the 3CL protease (3CLpro) is thought to be an ideal therapeutic agent against SARS, MERS, or COVID-19. Among these, SARS-CoV is the first corona-virus isolated and has been studied in detail since the first pandemic in 2003. This article briefly reviews a series of studies on SARS-CoV, focusing on the development of inhibitors for the SARS-CoV 3CLpro based on molecular interactions with the 3CL protease. Our recent approach, based on the structure-based rational design of a novel scaffold for SARS-CoV 3CLpro inhibitor, is also included. The achievements summarized in this short review would be useful for the design of a variety of novel inhibitors for corona-viruses, including SARS-CoV-2.


Assuntos
Antivirais/química , Betacoronavirus/química , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Inibidores de Proteases/química , Vírus da SARS/patogenicidade , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/classificação , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/enzimologia , Domínio Catalítico , Infecções por Coronavirus/tratamento farmacológico , Cristalografia por Raios X , Cisteína Endopeptidases/química , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Humanos , Cinética , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteases/classificação , Inibidores de Proteases/uso terapêutico , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Vírus da SARS/genética , Vírus da SARS/metabolismo , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Especificidade por Substrato , Termodinâmica , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
17.
Molecules ; 25(17)2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: covidwho-740497

RESUMO

A pandemic caused by the novel coronavirus (SARS-CoV-2 or COVID-19) began in December 2019 in Wuhan, China, and the number of newly reported cases continues to increase. More than 19.7 million cases have been reported globally and about 728,000 have died as of this writing (10 August 2020). Recently, it has been confirmed that the SARS-CoV-2 main protease (Mpro) enzyme is responsible not only for viral reproduction but also impedes host immune responses. The Mpro provides a highly favorable pharmacological target for the discovery and design of inhibitors. Currently, no specific therapies are available, and investigations into the treatment of COVID-19 are lacking. Therefore, herein, we analyzed the bioactive phytocompounds isolated by gas chromatography-mass spectroscopy (GC-MS) from Tinospora crispa as potential COVID-19 Mpro inhibitors, using molecular docking study. Our analyses unveiled that the top nine hits might serve as potential anti-SARS-CoV-2 lead molecules, with three of them exerting biological activity and warranting further optimization and drug development to combat COVID-19.


Assuntos
Antivirais/química , Betacoronavirus/química , Compostos Fitoquímicos/química , Inibidores de Proteases/química , Tinospora/química , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/classificação , Antivirais/isolamento & purificação , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/enzimologia , Domínio Catalítico , Infecções por Coronavirus/tratamento farmacológico , Cisteína Endopeptidases/química , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Descoberta de Drogas , Cromatografia Gasosa-Espectrometria de Massas , Expressão Gênica , Humanos , Cinética , Simulação de Acoplamento Molecular , Pandemias , Compostos Fitoquímicos/classificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteases/classificação , Inibidores de Proteases/isolamento & purificação , Inibidores de Proteases/farmacologia , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , Especificidade por Substrato , Termodinâmica , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
18.
Phys Rev Lett ; 125(5): 058001, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32794838

RESUMO

Glassy, nonexponential relaxations in globular proteins are typically attributed to conformational behaviors that are missing from intrinsically disordered proteins. Yet, we show that single molecules of a disordered-protein construct display two signatures of glassy dynamics, logarithmic relaxations and a Kovacs memory effect, in response to changes in applied tension. We attribute this to the presence of multiple independent local structures in the chain, which we corroborate with a model that correctly predicts the force dependence of the relaxation. The mechanism established here likely applies to other disordered proteins.


Assuntos
Modelos Químicos , Proteínas de Neurofilamentos/química , Cisteína/química , Cinética , Dobramento de Proteína , Termodinâmica
19.
Phys Rev Lett ; 125(6): 068102, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32845671

RESUMO

We quantified the equilibrium (un)folding free energy ΔG_{0} of an eight-amino-acid region starting from the fully folded state of the model membrane-protein bacteriorhodopsin using single-molecule force spectroscopy. Analysis of equilibrium and nonequilibrium data yielded consistent, high-precision determinations of ΔG_{0} via multiple techniques (force-dependent kinetics, Crooks fluctuation theorem, and inverse Boltzmann analysis). We also deduced the full 1D projection of the free-energy landscape in this region. Importantly, ΔG_{0} was determined in bacteriorhodopsin's native bilayer, an advance over traditional results obtained by chemical denaturation in nonphysiological detergent micelles.


Assuntos
Bacteriorodopsinas/química , Modelos Químicos , Microscopia de Força Atômica , Dobramento de Proteína , Termodinâmica
20.
Phys Rev Lett ; 125(7): 078102, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32857533

RESUMO

Diffusion-mediated surface phenomena are crucial for human life and industry, with examples ranging from oxygen capture by lung alveolar surface to heterogeneous catalysis, gene regulation, membrane permeation, and filtration processes. Their current description via diffusion equations with mixed boundary conditions is limited to simple surface reactions with infinite or constant reactivity. In this Letter, we propose a probabilistic approach based on the concept of boundary local time to investigate the intricate dynamics of diffusing particles near a reactive surface. Reformulating surface-particle interactions in terms of stopping conditions, we obtain in a unified way major diffusion-reaction characteristics such as the propagator, the survival probability, the first-passage time distribution, and the reaction rate. This general formalism allows us to describe new surface reaction mechanisms such as for instance surface reactivity depending on the number of encounters with the diffusing particle that can model the effects of catalyst fooling or membrane degradation. The disentanglement of the geometric structure of the medium from surface reactivity opens far-reaching perspectives for modeling, optimization, and control of diffusion-mediated surface phenomena.


Assuntos
Modelos Biológicos , Modelos Químicos , Membrana Celular/química , DNA/química , Difusão , Proteínas/química , Propriedades de Superfície , Termodinâmica
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