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1.
Pharmaceutical Technology Europe ; 33(1):20, 2021.
Article in English | ProQuest Central | ID: covidwho-20239803

ABSTRACT

Several medicines were approved as first treatments, including Gilead Sciences' Veklury (remdesivir) for patients with COVID-19 who require hospitalization (4);Amivas' artesunate for injection for severe malaria (5);Horizon Therapeutics Ireland DAC's Tepezza (teprotumumab-trbw), an antibody drug conjugate (ADC) for treating thyroid eye disease (6);and Ultragenyx Pharmaceutical's Dojolvi (triheptanoin) and Alnylam Pharmaceuticals' Oxlumo (lumasiran), both first treatments for metabolic disorders-Dojolvi for treating paediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (7) and Oxlumo (lumasiran) for treating the rare genetic disorder, primary hyperoxaluria type 1 (8). Blueprint Medicines Corporation) for treating unresectable or metastatic gastrointestinal stromal tumours harboring a platelet-derived growth factor receptor alpha exon 18 mutation (9);Koselugo (selumetinib, AstraZeneca Pharmaceuticals), for neurofibromatosis type 1 (10);Pemazyre (pemigatinib, Incyte Corporation), for certain types of previously treated, advanced bile duct cancer (cholangiocarcinoma) (11);Tabrecta (capmatinib, Novartis) for non-small cell lung cancer that has spread to other parts of the body and whose tumours have mutations that lead to MET exon 14 skipping (12);and Retevmo (selpercatinib, Loxo Oncology, a subsidiary of Eli Lilly and Company) for treating three types of tumours with alterations of the "rearranged during transfection" gene (13). Gilead, "U.S. FDA Approves Kite's Tecartus, the First and Only CAR T Treatment for Relapsed or Refractory Mantle Cell Lymphoma," Press Release, 24 July 2020.

2.
Food Frontiers ; 4(2):721-732, 2023.
Article in English | ProQuest Central | ID: covidwho-20238791

ABSTRACT

Foodstuff is a complex system that consists of a variety of nutrients. Protein is the basis of human life and health, which is made up of amino acids combined in different proportional orders. Polyphenols are a class of small molecule active substances with strong pro-life health effects. It has been found that protein and polyphenols can be combined by covalent and non-covalent interactions to form complex delivery carriers. The interaction between the two can effectively improve the physiological activities of proteins and enhance the bio-accessibility of polyphenols. With the maturation of ultrasound technology, several studies have shown that ultrasound can promote the production of protein−polyphenol complexes. To promote the study of protein–polyphenol interactions in foodstuff by ultrasound technology, the preparation methods of protein−polyphenol complexes, the effects of ultrasound on complex generation, and analytical methods were systematically summarized based on an extensive literature review, and further research directions were proposed. It provides the reference for the ultrasound study of protein−polyphenol complexes.

3.
The Treatment of Pharmaceutical Wastewater: Innovative Technologies and the Adaptation of Treatment Systems ; : 247-275, 2023.
Article in English | Scopus | ID: covidwho-20238410

ABSTRACT

During a coronavirus pandemic, the use of drugs that subsequently enter and contaminate water resources increases significantly. Water contaminated with pharmaceutical substances becomes dangerous to human health and threatens the functioning of all ecosystems. The use of various methods of wastewater treatment and solving this problem are still ongoing, so this chapter is devoted to one of the improved method that provides a synergistic effect of removing drugs from wastewaters. Advanced oxidation processes are popular for water purification, but their use is expensive, accompanied by the consumption of large amounts of electricity, and requires expensive materials. The combination of such methods with adsorption can reduce operating costs and increase process productivity, so the use of a hybrid oxidation process and adsorption is an excellent alternative for water purification from pharmaceuticals. The book chapter describes the main advantages and disadvantages of advanced oxidation processes (photocatalysis, ozonation, electrochemical oxidation, and Fenton processes). The adsorption process and effective materials used as adsorbents are described. The most common combinations of oxidation and adsorption processes, that generate active radicals, interact with a potential contaminant adsorbed on the adsorbent surface and decompose them to CO2 and H2O, are demonstrated. Hybrid methods of photocatalysis, Fenton process, ozonation and adsorption are presented, their mechanism and advantages over conventional methods in water purification from pharmaceutical compounds are described. The application of photocatalysis and adsorption is covered in details, and materials with photocatalytic properties and high surface area (iron oxides, titanium(IV) oxide, and zinc oxide) are characterized. As a result, the hybrid methods are considered effective for wastewater treatment from pharmaceutical contaminants. © 2023 Elsevier Inc. All rights reserved.

4.
New Journal of Chemistry ; 2023.
Article in English | EMBASE | ID: covidwho-20238253

ABSTRACT

A novel phenoxy-bridged trinuclear nickel(ii) complex [Ni3(mu-L)2(bipy)3](1) (where H3L= (E)-2-hydroxy-N-(2-hydroxy-3,5-diiodophenyl)-3,5-diiodobenzohydrazonic acid, bipy = 2,2'-bipyridyl) has been designed and synthesized as a potential antivirus drug candidate. The trinuclear Ni(ii) complex [Ni3(mu-L)2(bipy)3](1) was fully characterized via single crystal X-ray crystallography. The unique structure of the trinuclear nickel(ii) complex crystallized in a trigonal crystal system with P3221 space group and revealed distorted octahedral coordination geometry around each Ni(ii) ion. The X-ray diffraction analysis established the existence of a new kind of trinuclear metal system containing nickel(ii)-nickel(ii) interactions with an overall octahedral-like geometry about the nickel(ii) atoms. The non-bonded Ni-Ni distance seems to be 3.067 and 4.455 A from the nearest nickel atoms. The detailed structural analysis and non-covalent supramolecular interactions are also investigated by single crystal structure analysis and computational approaches. Hirshfeld surfaces (HSs) and 2D fingerprint plots (FPs) have been explored in the crystal structure to investigate the intermolecular interactions. The preliminary analysis of redox and magnetic characterization was conducted using cyclic voltammetry measurements and a vibrating sample magnetometer (VSM), respectively. This unique structure shows good inhibition performance for SARS-CoV-2, Omicron and HIV viruses. For insight into the potential application of the Ni(ii) coordination complex as an effective antivirus drug, we have examined the molecular docking of the trinuclear Ni(ii) complex [Ni3(mu-L)2(bipy)3](1) with the receptor binding domain (RBD) from SARS-CoV-2 (PDB ID: 7MZF), Omicron BA.3 variant spike (PDB ID: 7XIZ), and HIV protease (PDB ID: 7WCQ) viruses. This structure shows good inhibition performance for SARS-CoV-2, Omicron S protein and HIV protease viruses;the binding energies (DELTAG) and the respective Ki/Kd (inhibition/dissociation constants) correlation values are -8.9 (2.373 muM or 2373 nM), -8.1 (1.218 muM or 1218 nM) and -7.9 (0.874 muM or 874 nM), respectively. The results could be used for rational drug design against SARS-CoV-2 Omicron variant and HIV protease viruses.Copyright © 2023 The Royal Society of Chemistry.

5.
Environ Pollut ; 333: 121986, 2023 Jun 12.
Article in English | MEDLINE | ID: covidwho-20245293

ABSTRACT

The consumption of disinfectants increased dramatically with the outbreak of the COVID-19 epidemic. Benzalkonium chloride (DDBAC), a cationic surfactant disinfectant for import and export cargoes, is used for effective degradation method. For DDBAC effective degradation, polyhedral Fe-Mn bimetallic catalyst of Prussian blue analogue (FeMn-CA300) was novelty developed for rapid peroxymonosulfate (PMS) activation. Results showed that the Fe/Mn redox and surface hydroxyl groups in the catalyst played an important role in the DDBAC-enhanced degradation. The removal effectiveness of 10 mg L-1 DDBAC was up to 99.4% in 80 min under the initial pH = 7, catalyst dosage of 0.4 g L-1, and PMS concentration of 15 mmol L-1. In addition, FeMn-CA300 had a wide pH applicability range. The results indicated that hydroxyls, sulfate radicals, and singlet oxygen could effectively improve the degradation efficiency, where sulfate radicals played a crucial role. Finally, the corresponding degradation path of DDBAC was further provided according to GC-MS results. The results of this study provide new insights into the degradation of DDBAC, thereby highlighting the great potential of FeMnca300/PMS to control refractory organic compounds in the aqueous phase.

6.
Journal of Hazardous Materials Advances ; : 100326, 2023.
Article in English | ScienceDirect | ID: covidwho-2327775

ABSTRACT

The COVID-19 pandemic signified an unprecedented driver of plastic pollution, mainly composed of single-use face masks (FMs). Aiming to understand their negative impact (whether aged or not)on the trophic chain, biotic (e.g., bio-incrustation) and abiotic factors (e.g., UV-light, mechanical abrasion) which affect the toxicological profile of FMs or their sub-products (mainly microplastics, MPs, and nanoplastics, PNPs) were studied. In addition to the capacity of FMs to be an immediate source of MPs/PNPs, according to reports in the scientific literature, they are also good substrates since they tend to facilitate the proliferation and transport of eukaryotic and prokaryotic organisms, pathogens such as the SARS-CoV-2 virus, contaminating water sources and facilitating the enrichment and spread of antibiotic resistance genes (ARG) in the environment. However, there is limited research on macrofouling and species dispersal. Therefore, the present review aimed to provide an updated and summarized analysis of the environmental and ecotoxicological contribution of this type of waste as well as literature regarding face mask degradation and MPs and/or PNPs release, interaction with biota, colonization in addition to recommendations for future studies.

7.
Free Radical Biology and Medicine ; 201(Supplement 1):46, 2023.
Article in English | EMBASE | ID: covidwho-2324939

ABSTRACT

Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response and ultimate tissue scarring. Energy balance may be crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs Metformin (AMPk activator) and Baicalin (Cpt1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID19 patients that had been previously treated with Metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ACC signaling increased mitochondrial function and decreased TGF-beta-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two new indole derivatives IND6 and IND8 with AMPK activating capacity. Consistently, a reduced stay in the intensive care unit was observed in COVID-19 patients previously exposed to Metformin. Baicalin also reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19, while in vitro both drugs improved mitochondrial function and prevented TGF-beta-induced renal epithelial cell dedifferentiation. Our results support that strategies based on energy supply may prove useful in the prevention of COVID-19-induced lung and renal damage.Copyright © 2023

8.
Journal of Physical Chemistry C ; 2023.
Article in English | Scopus | ID: covidwho-2318837

ABSTRACT

The integrative study of the pharmacokinetics and dynamics of a drug has been of great research interest due to its authentic description of the biomedical and clinical pros and cons. Acetaminophen (N-acetyl-4-aminophenol, AcAP) is a well-known analgesic having a high therapeutic value, including the Covid-19 treatment. However, an overdose of the drug (>200 mg/kg of men) can lead to liver toxicity. An intermediate, N-acetyl-p-benzoquinone imine (NAPQI), metabolite formation has been found to be responsible for the toxicity. For the detection of NAPQI, several ex situ techniques based on electrochemical methods followed by nuclear magnetic resonance, high-performance liquid chromatography, and LC-MS were stated. For the first time, we report an in situ electrochemical approach for AcAP oxidation and NAPQI intermediate (Mw = 149.1 g mol-1) trapping on a graphitic nanomaterial, carbon black (CB)-modified electrode in pH 7 phosphate buffer solution (CB@NAPQI). The NAPQI-trapped electrode exhibited a surface-confined redox peak at E°′ = 0.350 ± 0.05 V vs Ag/AgCl with a surface excess value of 3.52 n mol cm-2. Physicochemical characterizations by scanning electron microscopy, Raman, FTIR, and in situ electrochemical quartz crystal microbalance (EQCM) techniques supported the entrapment of the molecular species. Furthermore, the scanning electrochemical microscopy (SECM) technique has been adopted for surface-mapping the true active site of the NAPQI-trapped electrode. As a biomimetic study, the mediated oxidation reaction of NADH by CB@NAPQI was demonstrated, and the mechanistic and quantitative aspects were studied using cyclic voltammetry, rotating disc electrode, amperometry, and flow injection analysis techniques. © 2023 American Chemical Society.

9.
Molecular Genetics and Metabolism ; 136(Supplement 1):S18, 2022.
Article in English | EMBASE | ID: covidwho-2318792

ABSTRACT

Background: Glycogen Storage Disease Ia (GSDIa) and Ib (GSDIb) are inborn errors of carbohydrate metabolism due to a deficiency of glucose-6-phosphatase (G6Pase) or glucose-6-phosphate translocase (G6PT), respectively. Consuming prescribed amounts of uncooked cornstarch (UCCS) to prevent hypoglycemia is the standard of care for GSDIa and GSDIb. Patients followed in our GSD Program are admitted to the hospital annually for evaluation of their metabolic control by measuring glucose and lactate levels and revising treatment regimens accordingly. Lack of bed space due to the COVID-19 pandemic has created a need for alternate markers of metabolic control as lactate measurements are unreliable in the outpatient setting. This research aims to identify alternative biomarkers to show degree of metabolic control in individuals with GSDI. Method(s): A retrospective chart review was conducted on 45 adults and children with GSDI using data from January 1, 2014 toMay 6, 2021. Plasma alanine and free carnitine levels were compared with laboratory reference ranges. Results from the three tests were not available on every subject. Plasma alanine was evaluated on 24 subjects (16-GSDIa, 8-GSDIb) and free carnitine was evaluated on 25 subjects (17-GSDIa, 8-GSDIb). Result(s): Alanine levels in subjects with GSDIa ranged from 378 to 786 umol/L, while alanine levels in subjects with GSDIb ranged from 254 to 506 umol/L (reference range = 103-528 umol/L). Free carnitine levels ranged from26 to 72 umol/L in subjects with GSDIa and from 44 to 90 umol/L in subjects with GSDIb (reference range = 19-55 umol/L). Conclusion(s): Our analysis showed that plasma alanine and free carnitine have potential to be used as biomarkers of metabolic control. For plasma alanine, there seemed to be differences between subjects with GSDIa and GSDIb, as the majority of subjects with GSDIa had elevations in plasma alanine, while subjects with GSDIb did not. Elevated plasma alanine levels indicate lactic acidosis. For GSDIb, we hypothesize that there may be some type of G6Pase enzyme activity that occurs outside of the endoplasmic reticulum. When looking at both groups, free carnitine levels were mostly elevated. This indicates that there could be inhibition of fatty acid oxidation.Copyright © 2022 Elsevier Inc. All rights reserved.

10.
Build Environ ; 240: 110422, 2023 Jul 15.
Article in English | MEDLINE | ID: covidwho-2319773

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2, the virus that causes the coronavirus disease (COVID)-19, is primarily transmitted through respiratory droplets which linger in enclosed spaces, often exacerbated by HVAC systems. Although research to improve HVAC handling of SARS-CoV-2 is progressing, currently installed HVAC systems cause problems because they recirculate air and use ineffective filters against virus. This paper details the process of developing a novel method of eliminating air pollutants and suspended pathogens in enclosed spaces using Photocatalytic Oxidation (PCO) technology. It has been previously employed to remove organic contaminants and compounds from air streams using the irradiation of titanium dioxide (TiO2) surfaces with ultraviolet (UV) lights causing the disintegration of organic compounds by reactions with oxygen (O) and hydroxyl radicals (OH). The outcome was two functional prototypes that demonstrate the operation of PCO-based air purification principle. These prototypes comprise a novel TiO2 coated fibre mop system, which provide very large surface area for UV irradiation. Four commercially accessible materials were used for the construction of the mop: Tampico, Brass, Coco, and Natural synthetic. Two types of UV lights were used: 365 nm (UVA) and 270 nm (UVC). A series of tests were conducted that proved the prototype's functionality and its efficiency in lowering volatile organic compounds (VOCs) and formaldehyde (HCHO). The results shown that a MopFan with rotary mop constructed with Coco fibres and utilising UVC light achieves the best VOC and HCHO purification performance. Within 2 h, this combination lowered HCHO by 50% and VOCs by 23% approximately.

11.
Particuology ; 80:157-169, 2023.
Article in English | Web of Science | ID: covidwho-2308417

ABSTRACT

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

12.
Chemical Engineering Journal ; 461, 2023.
Article in English | Web of Science | ID: covidwho-2307871

ABSTRACT

Anodic aluminium oxide-copper (AAO-Cu) coatings were prepared on the aluminium (Al) alloy substrates to attain excellent antibacterial performance and mechanical stability. The nanoporous AAO interlayer was ob-tained by anodic oxidation with an outer Cu layer deposited by electroplating. The intermediate zone (similar to 2 mu m thick) of the AAO-Cu coating plays a significant role in the coating properties. The interlocking effect in the AAO-Cu intermediate zone significantly enhances the coating adhesion and curbs the coating defoliation. The anti-bacterial tests show that the AAO-Cu zone provides excellent antibacterial ability even when the outer Cu coating was removed. The sustained antibacterial rate of the AAO-Cu intermediate zone against E. coli exceeded 95%. The Cu ions released from the embedded Cu in the nanoporous AAO structure ensure a long-term antibacterial capability. This coating system can be promoted in a large wide range of antibacterial products in public.

13.
Journal of the Brazilian Chemical Society ; 2023.
Article in English | Web of Science | ID: covidwho-2310779

ABSTRACT

The efforts of contrasting the effects caused by the Covid-19 (coronavirus disease 2019) pandemic increased the disposal of active pharmaceutical ingredients. This paper reports the mechanisms and kinetics of the degradation in aqueous environments induced by 'OH of two drugs, among those most widely probed at the outbreak of coronavirus, nitazoxanide and hydroxychloroquine. The investigation exploits quantum chemistry techniques and a reaction rate theory combined with diffusion-controlled processes and quantum mechanical tunneling. The reaction rate constants are obtained in an environmentally relevant temperature range. The results show that (i) the deacetylation of nitazoxanide with formation of tizoxanide is kinetically the most favorable channel, in agreement with experimental work;(ii) for hydroxychloroquine, the present theoretical calculations show that the most favorable channel is the addition of 'OH at the aromatic ring. The half-life time degradation products are for both cases in the range between 12 to 138 days. Both drugs presented toxicities between harmful and toxic as obtained by computational toxicology calculations: The toxicity is also calculated for the degradation products: (i) in the nitazoxanide degradation process, tizoxanide was characterized as more toxic, while (ii) in the case of hydroxychloroquine, the major degradation product showed a decrease in the toxicity.

14.
Indian Drugs ; 59(12):55-69, 2022.
Article in English | EMBASE | ID: covidwho-2289722

ABSTRACT

Molnupiravir, a broad-spectrum antiviral is an isopropyl ester prodrug of beta-D-N4-hydroxycytidine. Molnupiravir targets RNA-dependent RNA-polymerase enzyme of the viruses. A new stability-indicating HPLC-method was developed to determine related substances and assay of molnupiravir. Separation was achieved by using Shim-pack GWS C18 column. The method was validated according to current ICH requirements. The calibration plot gave a linear relationship for all known analytes over the concentration range from LOQ to 200%. LOD and LOQ for all known analytes were found in 0.05-0.08 microg mL-1 and 0.12-0.20 microg mL-1, respectively, the mean recovery was found to be 97.79-102.44 %. Study showed that the method, results of robustness, solution stability studies are precise and within the acceptable limits. Molnupiravir was found to degrade in acid, alkali, and oxidative conditions, and was stable in thermal, moisture, and photolytic degradation condition. The method is simple, accurate, precise, and reproducible for routine purity analysis of drug-samples.Copyright © 2022 Indian Drug Manufacturers' Association. All rights reserved.

15.
Nat Prod Res ; : 1-5, 2021 Dec 02.
Article in English | MEDLINE | ID: covidwho-2293741

ABSTRACT

Facile two-pot total synthesis of baphicacanthin A, a natural phenoxazinone alkaloid isolated from the roots of Baphicacanthus cusia which has been utilized as a traditional chinese medicine to effectively treat disease caused by coronavirus, has been developed from simple and commercially available starting materials. Catalytic aerobic oxidative cross-cyclocondensation of equimolar 2-aminophenol and 3-methoxy-2-hydroxylphenol in water was used to construct the key molecular skeleton 2-hydroxy-3H-phenoxazin-3-one. Gram scale synthesis was realized in 80% overall yield with practical convenience.

16.
ACS Sens ; 8(5): 2011-2020, 2023 05 26.
Article in English | MEDLINE | ID: covidwho-2298962

ABSTRACT

Single-particle collision electrochemistry (SPCE) has shown great promise in biosensing applications due to its high sensitivity, high flux, and fast response. However, a low effective collision frequency and a large number of interfering substances in complex matrices limit its broad application in clinical samples. Herein, a novel and universal SPCE biosensor was proposed to realize sensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on the collision and oxidation of single silver nanoparticles (Ag NPs) on polysulfide-functionalized gold ultramicroelectrodes (Ps-Au UMEs). Taking advantage of the strong interaction of the Ag-S bond, collision and oxidation of Ag NPs on the Ps-Au UME surface could be greatly promoted to generate enhanced Faraday currents. Compared with bare Au UMEs, the collision frequency of Ps-Au UMEs was increased by 15-fold, which vastly improved the detection sensitivity and practicability of SPCE in biosensing. By combining magnetic separation, liposome encapsulation release, and DNAzyme-assisted signal amplification, the SPCE biosensor provided a dynamic range of 5 orders of magnitude for spike proteins with a detection limit of 6.78 fg/mL and a detection limit of 21 TCID50/mL for SARS-CoV-2. Furthermore, SARS-CoV-2 detection in nasopharyngeal swab samples of infected patients was successfully conducted, indicating the potential of the SPCE biosensor for use in clinically relevant diagnosis.


Subject(s)
COVID-19 , Metal Nanoparticles , Humans , SARS-CoV-2 , Microelectrodes , Metal Nanoparticles/chemistry , COVID-19/diagnosis , Electrochemistry , Silver
17.
Eur J Med Chem ; 244: 114853, 2022 Dec 15.
Article in English | MEDLINE | ID: covidwho-2301653

ABSTRACT

SARS-CoV-2 caused worldwide the current outbreak called COVID-19. Despite multiple countermeasures implemented, there is an urgent global need for new potent and efficient antiviral drugs against this pathogen. In this context, the main protease (Mpro) of SARS-CoV-2 is an essential viral enzyme and plays a pivotal role in viral replication and transcription. Its specific cleavage of polypeptides after a glutamine residue has been considered as a key element to design novel antiviral drugs. Herein, we reported the design, synthesis and structure-activity relationships of novel α-ketoamides as covalent reversible inhibitors of Mpro, exploiting the PADAM oxidation route. The reported compounds showed µM to nM activities in enzymatic and in the antiviral cell-based assays against SARS-CoV-2 Mpro. In order to assess inhibitors' binding mode, two co-crystal structures of SARS-CoV-2 Mpro in complex with our inhibitors were solved, which confirmed the covalent binding of the keto amide moiety to the catalytic Cys145 residue of Mpro. Finally, in order to interrogate potential broad-spectrum properties, we assessed a selection of compounds against MERS Mpro where they showed nM inhibitory potency, thus highlighting their potential as broad-spectrum coronavirus inhibitors.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Humans , Coronavirus 3C Proteases , Protease Inhibitors/pharmacology , Protease Inhibitors/chemistry , Viral Nonstructural Proteins , Cysteine Endopeptidases/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Molecular Docking Simulation
18.
Chemical Engineering Journal ; 426(49), 2021.
Article in English | CAB Abstracts | ID: covidwho-2269792

ABSTRACT

Triclosan (TCS) has been proved to have a harmful effect on human health and ecological environment, especially during the COVID-19 epidemic, when plentiful antibacterial hand sanitizers were discharged. Manganese dioxide (MnO2) showed a good effect on the removal of TCS. The morphology of MnO2 was regulated in this study to increase the active sites for removing TCS and improve the removal effect. The results showed that nanoflower T-MnO2 exhibited best removal efficiency due to its high oxygen vacancy, high Mn3+ content, easily released lattice oxygen and unique tunnel structure which make its Mn-O bond easier to activate. Further study of the mechanism revealed that the process of removing TCS by MnO2 was the first adsorption and then oxidation process and the detailed reaction process was clarified. 3-chlorophenol and 2,4-dichlorophenol were proved to be their oxidative product. Additionally, it was verified that oxidation dominated in the removal of TCS by MnO2 rather than adsorption through Density functional theory (DFT) calculations analysis. It is determined that nanoflower MnO2 was a promising material for removing TCS.

19.
Chemosensors ; 11(2):149, 2023.
Article in English | ProQuest Central | ID: covidwho-2267936

ABSTRACT

Conventional enzyme-based continuous glucose sensors in interstitial fluid usually rely on dissolved oxygen as the electron-transfer mediator to bring electrons from oxidase to electrode while generating hydrogen peroxide. This may lead to several problems. First, the sensor may provide biased detection results owing to fluctuation of oxygen in interstitial fluid. Second, the polymer coatings that regulate the glucose/oxygen ratio can affect the dynamic response of the sensor. Third, the glucose oxidation reaction continuously produces corrosive hydrogen peroxide, which may compromise the long-term stability of the sensor. Here, we introduce an oxygen-independent nonenzymatic glucose sensor based on water splitting-assisted electrocatalysis for continuous glucose monitoring. For the water splitting reaction (i.e., hydrogen evolution reaction), a negative pretreatment potential is applied to produce a localized alkaline condition at the surface of the working electrode for subsequent nonenzymatic electrocatalytic oxidation of glucose. The reaction process does not require the participation of oxygen;therefore, the problems caused by oxygen can be avoided. The nonenzymatic sensor exhibits acceptable sensitivity, reliability, and biocompatibility for continuous glucose monitoring in hypoxic environments, as shown by the in vitro and in vivo measurements. Therefore, we believe that it is a promising technique for continuous glucose monitoring, especially for clinically hypoxic patients.

20.
International Food Research Journal ; 30(1):63-78, 2023.
Article in English | ProQuest Central | ID: covidwho-2262177
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