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1.
Biochem J ; 479(20): 2175-2193, 2022 Oct 28.
Article in English | MEDLINE | ID: covidwho-2062282

ABSTRACT

Coronaviruses have been responsible for multiple challenging global pandemics, including coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Papain-like protease (PLpro), one of two cysteine proteases responsible for the maturation and infectivity of SARS-CoV-2, processes and liberates functional proteins from the viral polyproteins and cleaves ubiquitin and ISG15 modifications to inhibit innate immune sensing. Consequently, PLpro is an attractive target for developing COVID-19 therapies. PLpro contains a zinc-finger domain important for substrate binding and structural stability. However, the impact of metal ions on the activity and biophysical properties of SARS-CoV-2 PLpro has not been comprehensively studied. Here, we assessed the impacts of metal ions on the catalytic activity of PLpro. Zinc had the largest inhibitory effect on PLpro, followed by manganese. Calcium, magnesium, and iron had smaller or no effects on PLpro activity. EDTA at a concentration of 0.5 mM was essential for PLpro activity, likely by chelating trace metals that inhibit PLpro. IC50 values for ZnCl2, ZnSO4, and MnCl2 of 0.42 ± 0.02 mM, 0.35 ± 0.01 mM, and 2.6 ± 0.3 mM were obtained in the presence of 0.5 mM EDTA; in the absence of EDTA, the estimated IC50 of ZnCl2 was 14 µM. Tryptophan intrinsic fluorescence analysis confirmed the binding of zinc and manganese to PLpro, and differential scanning calorimetry revealed that zinc but not manganese reduced ΔHcal of PLpro. The results of this study provide a reference for further work targeting PLpro to prevent and treat COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Papain/chemistry , Papain/metabolism , COVID-19/drug therapy , Peptide Hydrolases/metabolism , Magnesium , Calcium , Tryptophan , Edetic Acid , Ubiquitin/metabolism , Polyproteins , Ions , Zinc , Iron
2.
Sci Rep ; 12(1): 16481, 2022 Oct 01.
Article in English | MEDLINE | ID: covidwho-2050552

ABSTRACT

Observations of air pollution in Krakow have shown that air quality has been improved during the last decade. In the presented study two factors affecting the physicochemical characteristic of PM2.5 fraction at AGH station in Krakow were observed. One is the ban of using solid fuels for heating purposes and the second is COVID-19 pandemic in Krakow. The PM2.5 fraction was collected during the whole year every 3rd day between 2nd March 2020 and 28th February 2021 at AGH station in Krakow. In total 110 PM2.5 fraction samples were collected. The chemical composition was determined for these samples. The elemental analysis was performed by energy dispersive X-ray fluorescence (EDXRF) technique, ions analysis was performed by ion chromatography (IC) and black carbon by optical method. In order to identify the emission sources the positive matrix factorization (PMF) was used. The results of such study were compared to similar analysis performed for PM2.5 for the period from June 2018 to May 2019 at AGH station in Krakow. The PM2.5 concentration dropped by 25% in 2020/2021 in comparison to 2018/2019 at this station. The concentrations of Si, K, Fe, Zn and Pb were lowering by 43-64% in the year 2020/2021 in comparison to 2018/2019. Cu, Mn, Zn and Pb come from mechanical abrasion of brakes and tires while Ti, Fe, Mn and Si are crustal species. They are the indicators of road dust (non-exhaust traffic source). Moreover, the annual average contribution of traffic/industrial/soil/construction work source was reduced in 2020/2021 in comparison to 2018/2019. As well the annual average contribution of fuels combustion was declining by 22% in 2020/2021 in comparison to 2018/2019. This study shows that the ban and lockdown, during COVID-19 pandemic, had significant impact on the characteristic of air pollution in Krakow.


Subject(s)
Air Pollutants , COVID-19 , Air Pollutants/analysis , COVID-19/epidemiology , Carbon/analysis , Communicable Disease Control , Dust/analysis , Environmental Monitoring/methods , Humans , Ions/analysis , Lead/analysis , Pandemics , Particulate Matter/analysis , Poland/epidemiology , Soil , Vehicle Emissions/analysis
3.
Inorg Chem ; 61(39): 15664-15677, 2022 Oct 03.
Article in English | MEDLINE | ID: covidwho-2036737

ABSTRACT

The identification of novel therapeutics against the pandemic SARS-CoV-2 infection is an indispensable new address of current scientific research. In the search for anti-SARS-CoV-2 agents as alternatives to the vaccine or immune therapeutics whose efficacy naturally degrades with the occurrence of new variants, the salts of Bi3+ have been found to decrease the activity of the Zn2+-dependent non-structural protein 13 (nsp13) helicase, a key component of the SARS-CoV-2 molecular tool kit. Here, we present a multilevel computational investigation based on the articulation of DFT calculations, classical MD simulations, and MIF analyses, focused on the examination of the effects of Bi3+/Zn2+ exchange on the structure and molecular interaction features of the nsp13 protein. Our calculations confirmed that Bi3+ ions can replace Zn2+ in the zinc-finger metal centers and cause slight but appreciable structural modifications in the zinc-binding domain of nsp13. Nevertheless, by employing an in-house-developed ATOMIF tool, we evidenced that such a Bi3+/Zn2+ exchange may decrease the extension of a specific hydrophobic portion of nsp13, responsible for the interaction with the nsp12 protein. The present study provides for a detailed, atomistic insight into the potential anti-SARS-CoV-2 activity of Bi3+ and, more generally, evidences the hampering of the nsp13-nsp12 interaction as a plausible therapeutic strategy.


Subject(s)
COVID-19 , SARS-CoV-2 , Bismuth , Humans , Ions , RNA Helicases/chemistry , RNA Helicases/metabolism , Salts , Zinc
4.
Rapid Commun Mass Spectrom ; 36(20): e9373, 2022 Oct 30.
Article in English | MEDLINE | ID: covidwho-2027400

ABSTRACT

RATIONALE: The COVID-19 pandemic demonstrated the importance of high-throughput analysis for public health. Given the importance of surface viral proteins for interactions with healthy tissue, they are targets of interest for mass spectrometry-based analysis. For that reason, the possibility of detecting and quantifying peptides using a high-throughput technique, laser diode thermal desorption-triple quadrupole mass spectrometry (LDTD-QqQMS), was explored. METHODS: Two peptides used as models for small peptides (leu-enkephalin and endomorphin-2) and four tryptic peptides (GVYYPDK, NIDGYFK, IADYNYK, and QIAPGQTGK) specific to the SARS-CoV-2 Spike protein were employed. Target peptides were analyzed individually in the positive mode by LDTD-QqQMS. Peptides were quantified by internal calibration using selected reaction monitoring transitions in pure solvents and in samples spiked with 20 µg mL-1 of a bovine serum albumin tryptic digest to represent real analysis conditions. RESULTS: Low-energy fragment ions (b and y ions) as well as high-energy fragment ions (c and x ions) and some of their corresponding water or ammonia losses were detected in the full mass spectra. Only for the smallest peptides, leu-enkephalin and endomorphin-2, were [M + H]+ ions observed. Product ion spectra confirmed that, with the experimental conditions used in the present study, LDTD transfers a considerable amount of energy to the target peptides. Quantitative analysis showed that it was possible to quantify peptides using LDTD-QqQMS with acceptable calibration curve linearity (R2 > 0.99), precision (RSD < 18.2%), and trueness (bias < 8.3%). CONCLUSIONS: This study demonstrated for the first time that linear peptides can be qualitatively and quantitatively analyzed using LDTD-QqQMS. Limits of quantification and dynamic ranges are still inadequate for clinical applications, but other applications where higher levels of proteins must be detected could be possible with LDTD. Given the high-throughput capabilities of LDTD-QqQMS (>15 000 samples in less than 43 h), more studies are needed to improve the sensitivity for peptide analysis of this technique.


Subject(s)
COVID-19 , Tandem Mass Spectrometry , Enkephalin, Leucine , Humans , Ions , Lasers , Pandemics , Peptides , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Tandem Mass Spectrometry/methods
5.
Int J Mol Sci ; 23(16)2022 Aug 12.
Article in English | MEDLINE | ID: covidwho-2023734

ABSTRACT

Heavy metal ions can disrupt biological functions via multiple molecular mechanisms, including inhibition of enzymes. We investigate the interactions of human papain-like cysteine endopeptidases cathepsins L, K, and S with gallium and cerium ions, which are associated with medical applications. We compare these results with zinc and lead, which are known to inhibit thiol enzymes. We show that Ga3+, Ce3+, and Ce4+ ions inhibit all tested peptidases with inhibition constants in the low micromolar range (between 0.5 µM and 10 µM) which is comparable to Zn2+ ions, whereas inhibition constants of Pb2+ ions are one order of magnitude higher (30 µM to 150 µM). All tested ions are linear specific inhibitors of cathepsin L, but cathepsins K and S are inhibited by Ga3+, Ce3+, and Ce4+ ions via hyperbolic inhibition mechanisms. This indicates a mode of interaction different from that of Zn2+ and Pb2+ ions, which act as linear specific inhibitors of all peptidases. All ions also inhibit the degradation of insoluble elastin, which is a common target of these peptidases in various inflammatory diseases. Our results suggest that these ions and their compounds have the potential to be used as cysteine cathepsin inhibitors in vitro and possibly in vivo.


Subject(s)
Cerium , Gallium , Cathepsin K/metabolism , Cathepsins/metabolism , Cysteine , Cysteine Proteinase Inhibitors/metabolism , Cysteine Proteinase Inhibitors/pharmacology , Endopeptidases/metabolism , Humans , Ions , Kinetics , Lead
6.
Sci Rep ; 12(1): 3794, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-2004784

ABSTRACT

SARS-CoV-2 virions enter the host cells by docking their spike glycoproteins to the membrane-bound Angiotensin Converting Enzyme 2. After intracellular assembly, the newly formed virions are released from the infected cells to propagate the infection, using the extra-cytoplasmic ACE2 docking mechanism. However, the molecular events underpinning SARS-CoV-2 transmission between host cells are not fully understood. Here, we report the findings of a scanning Helium-ion microscopy study performed on Vero E6 cells infected with mNeonGreen-expressing SARS-CoV-2. Our data reveal, with unprecedented resolution, the presence of: (1) long tunneling nanotubes that connect two or more host cells over submillimeter distances; (2) large scale multiple cell fusion events (syncytia); and (3) abundant extracellular vesicles of various sizes. Taken together, these ultrastructural features describe a novel intra-cytoplasmic connection among SARS-CoV-2 infected cells that may act as an alternative route of viral transmission, disengaged from the well-known extra-cytoplasmic ACE2 docking mechanism. Such route may explain the elusiveness of SARS-CoV-2 to survive from the immune surveillance of the infected host.


Subject(s)
Microscopy/methods , SARS-CoV-2/physiology , Virus Internalization , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/transmission , COVID-19/virology , Chlorocebus aethiops , Cytoplasm/chemistry , Cytoplasm/ultrastructure , Cytoplasm/virology , Extracellular Vesicles/chemistry , Extracellular Vesicles/ultrastructure , Giant Cells/chemistry , Giant Cells/physiology , Helium/chemistry , Humans , Ions/chemistry , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells
7.
Langmuir ; 38(30): 9186-9194, 2022 08 02.
Article in English | MEDLINE | ID: covidwho-1947187

ABSTRACT

The spike (S) protein of SARS-CoV-2 has been found to play a decisive role in the cell entry mechanism of the virus and has been the prime target of most vaccine development efforts. Although numerous vaccines are already in use and more than half of the world population has been fully vaccinated, the emergence of new variants of the virus poses a challenge to the existing vaccines. Hence, developing an effective drug therapy is a crucial step in ending the pandemic. Nanoparticles can play a crucial role as a drug or a drug carrier and help tackle the pandemic effectively. Here, we performed explicit all-atom molecular dynamics simulations to probe interactions between S protein and Montmorillonite (MMT) nano clay surface. We built two systems with different counterions (Na+ and Ca2+), namely Na-MMT and Ca-MMT, to investigate the effect of different ions on S protein-MMT interaction. Structural modification of S protein was observed in the presence of MMT surface, particularly the loss of helical content of S protein. We revealed that electrostatic and hydrophobic interactions synergistically govern the S protein-MMT interactions. However, hydrophobic interactions were more pronounced in the Na-MMT system than in Ca-MMT. We also revealed residues and glycans of S protein closely interacting with the MMT surface. Interestingly, N165 and N343, which we found to be closely interacting with MMT in our simulations, also have a critical role in cell entry and in thwarting the cell's immune response in recent studies. Overall, our work provides atomistic insights into S protein-MMT interaction and enriches our understanding of the nanoparticle-S protein interaction mechanism, which will help develop advanced therapeutic techniques in the future.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Bentonite/chemistry , Humans , Ions , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism
8.
Int J Mol Sci ; 21(16)2020 Aug 06.
Article in English | MEDLINE | ID: covidwho-1934101

ABSTRACT

The recently discovered 340-cavity in influenza neuraminidase (NA) N6 and N7 subtypes has introduced new possibilities for rational structure-based drug design. However, the plasticity of the 340-loop (residues 342-347) and the role of the 340-loop in NA activity and substrate binding have not been deeply exploited. Here, we investigate the mechanism of 340-cavity formation and demonstrate for the first time that seven of nine NA subtypes are able to adopt an open 340-cavity over 1.8 µs total molecular dynamics simulation time. The finding that the 340-loop plays a role in the sialic acid binding pathway suggests that the 340-cavity can function as a druggable pocket. Comparing the open and closed conformations of the 340-loop, the side chain orientation of residue 344 was found to govern the formation of the 340-cavity. Additionally, the conserved calcium ion was found to substantially influence the stability of the 340-loop. Our study provides dynamical evidence supporting the 340-cavity as a druggable hotspot at the atomic level and offers new structural insight in designing antiviral drugs.


Subject(s)
Antiviral Agents/pharmacology , Drug Development , Neuraminidase/chemistry , Orthomyxoviridae/enzymology , Binding Sites , Calcium/chemistry , Ions , Models, Molecular , Molecular Dynamics Simulation , N-Acetylneuraminic Acid/chemistry , Principal Component Analysis , Protein Structure, Secondary , Thermodynamics
9.
Cells ; 11(13)2022 06 23.
Article in English | MEDLINE | ID: covidwho-1933986

ABSTRACT

Two pore channels (TPCs) are implicated in vesicle trafficking, virus infection, and autophagy regulation. As Na+- or Ca2+-permeable channels, TPCs have been reported to be activated by NAADP, PI(3,5)P2, and/or high voltage. However, a comparative study on the function and regulation of the three mammalian TPC subtypes is currently lacking. Here, we used the electrophysiological recording of enlarged endolysosome vacuoles, inside-out and outside-out membrane patches to examine the three TPCs of rabbit (Oryctolagus cuniculus, or Oc) heterologously expressed in HEK293 cells. While PI(3,5)P2 evoked Na+ currents with a potency order of OcTPC1 > OcTPC3 > OcTPC2, only OcTPC2 displayed a strict dependence on PI(3,5)P2. Both OcTPC1 and OcTPC3 were activatable by PI3P and OcTPC3 was also activated by additional phosphoinositide species. While OcTPC2 was voltage-independent, OcTPC1 and OcTPC3 showed voltage dependence with OcTPC3 depending on high positive voltages. Finally, while OcTPC2 preferred a luminal pH of 4.6-6.0 in endolysosomes, OcTPC1 was strongly inhibited by extracytosolic pH 5.0 in both voltage-dependent and -independent manners, and OcTPC3 was inhibited by pH 6.0 but potentiated by pH 8.0. Thus, the three OcTPCs form phosphoinositide-activated Na+ channels with different ligand selectivity, voltage dependence, and extracytosolic pH sensitivity, which likely are optimally tuned for function in specific endolysosomal populations.


Subject(s)
Lysosomes , Phosphatidylinositols , Animals , HEK293 Cells , Humans , Hydrogen-Ion Concentration , Ions , Mammals , Phosphatidylinositol Phosphates , Rabbits
10.
World J Microbiol Biotechnol ; 38(9): 158, 2022 Jul 12.
Article in English | MEDLINE | ID: covidwho-1930505

ABSTRACT

In this mini-review, after a brief introduction into the widespread antimicrobial use of silver ions and nanoparticles against bacteria, fungi and viruses, the toxicity of silver compounds and the molecular mechanisms of microbial silver resistance are discussed, including recent studies on bacteria and fungi. The similarities and differences between silver ions and silver nanoparticles as antimicrobial agents are also mentioned. Regarding bacterial ionic silver resistance, the roles of the sil operon, silver cation efflux proteins, and copper-silver efflux systems are explained. The importance of bacterially produced exopolysaccharides as a physiological (biofilm) defense mechanism against silver nanoparticles is also emphasized. Regarding fungal silver resistance, the roles of metallothioneins, copper-transporting P-type ATPases and cell wall are discussed. Recent evolutionary engineering (adaptive laboratory evolution) studies are also discussed which revealed that silver resistance can evolve rapidly in bacteria and fungi. The cross-resistance observed between silver resistance and resistance to other heavy metals and antibiotics in bacteria and fungi is also explained as a clinically and environmentally important issue. The use of silver against bacterial and fungal biofilm formation is also discussed. Finally, the antiviral effects of silver and the use of silver nanoparticles against SARS-CoV-2 and other viruses are mentioned. To conclude, silver compounds are becoming increasingly important as antimicrobial agents, and their widespread use necessitates detailed understanding of microbial silver response and resistance mechanisms, as well as the ecological effects of silver compounds. Figure created with BioRender.com.


Subject(s)
Anti-Infective Agents , Bacterial Infections , COVID-19 , Metal Nanoparticles , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/metabolism , Anti-Infective Agents/pharmacology , Bacteria/metabolism , Copper/metabolism , Humans , Ions/metabolism , Ions/pharmacology , SARS-CoV-2 , Silver/metabolism , Silver/pharmacology , Silver Compounds/metabolism , Silver Compounds/pharmacology
11.
Bull Environ Contam Toxicol ; 108(5): 819-823, 2022 May.
Article in English | MEDLINE | ID: covidwho-1919758

ABSTRACT

Fine particulate matter (named PM2.5) has become a prominent and dangerous form of air pollution. The chemical composition of PM2.5 mainly includes inorganic elements, water soluble ions, elemental carbon (EC), organic carbon (OC), and organic compounds. The detection method for inorganic elements mainly includes X ray fluorescence, inductively coupled plasma-atomic emission spectrometry, and inductively coupled plasma mass spectrometry. As for water soluble ions, ion chromatography is the most common detection method. EC and OC are usually detected by carbon analyzer. The organic compounds are determined by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. In this paper, the merits and drawbacks of each analytical methods for the determination of PM2.5 chemical composition are summarized. This review also includes our discussion on the improvement of the analytical accuracy for the determination of PM2.5 chemical composition owing to the development of reference materials.


Subject(s)
Air Pollutants , Aerosols/analysis , Air Pollutants/analysis , Carbon/analysis , China , Environmental Monitoring/methods , Ions/analysis , Organic Chemicals/analysis , Particulate Matter/analysis , Seasons , Water/chemistry
12.
J Trace Elem Med Biol ; 73: 127015, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1867436

ABSTRACT

OBJECTIVE: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), a worldwide health problem, is the cause of 2019 coronavirus disease. This study aimed to compare the trace element (selenium and iron), electrolyte (calcium and sodium), and physical activity levels of COVID-19 patients before and after COVID-19 treatment. METHOD: This prospective study was conducted in patients diagnosed with COVID-19 (n = 15). Trace element (selenium and iron), electrolyte (calcium and sodium), and physical activity levels of the patients were compared before and after the treatment. RESULT: Most of patients had selenium deficiency (86.7 %), iron deficiency (73.3 %), calcium deficiency (66.7 %) and sodium deficiency (46.7 %) before COVID-19 treatment. The most important improvements were seen in iron deficiency (from 73.3 % to 26.7 %) and sodium deficiency (from 46.7 % to 13.3 %) after the treatment. Selenium, iron, calcium, and sodium levels of the patients were significantly higher after the treatment (p < 0.05). The patients had low physical activity before and after COVID-19 treatment. In addition, no statistically significant difference was found in the comparison of physical activity levels (p > 0.05). CONCLUSION: This study indicated that selenium, iron, calcium, and sodium levels and deficiencies might improve after treating patients with COVID-19. However, the results of this study showed that the physical activity levels of COVID-19 patients might remain stable and low throughout the treatment process.


Subject(s)
COVID-19 , Selenium , Trace Elements , COVID-19/drug therapy , Calcium , Electrolytes , Exercise , Humans , Ions , Iron , Prospective Studies , SARS-CoV-2 , Selenium/therapeutic use , Sodium , Trace Elements/therapeutic use
13.
Front Cell Infect Microbiol ; 12: 897416, 2022.
Article in English | MEDLINE | ID: covidwho-1847157

ABSTRACT

The pandemic of respiratory diseases, such as coronavirus disease 2019 (COVID-19) and influenza, has imposed significant public health and economic burdens on the world. Wearing masks is an effective way to cut off the spread of the respiratory virus. However, due to cultural differences and uncomfortable wearing experiences, not everyone is willing to wear masks; there is an urgent need to find alternatives to masks. In this study, we tested the disinfection effect of a portable ionizer on pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (strain V34) and influenza A virus (strain CA04). Negative ions significantly reduced the concentration of particulate matter in the air above and effectively disinfected viruses stuck to the solid plate at the level of both nucleic acid and virus titer. The disinfection efficiency was >99.8% after 1-h exposure. Moreover, negative ions effectively disinfected aerosolized viruses; the disinfection efficiency was more than 87.77% after purification for 10 min. Furthermore, negative ions had a significant protective effect on susceptible animals exposed to viral aerosols. When the negative ionizer was switched from off to on, the inhalation 50% infective dose (ID50) for golden hamsters challenged with SARS-CoV-2 rose from 9.878 median tissue culture infective dose (TCID50) [95% confidence interval (CI), 6.727-14.013 TCID50] to 43.891 TCID50 (95% CI, 29.31-76.983 TCID50), and the inhalation ID50 for guinea pigs challenged with influenza A virus rose from 6.696 TCID50 (95% CI, 3.251-9.601 TCID50) to 28.284 TCID50 (95% CI, 19.705-40.599 TCID50). In the experiment of transmission between susceptible animals, negative ions 100% inhibited the aerosol transmission of SARS-CoV-2 and influenza A virus. Finally, we tested the safety of negative ion exposure. Balb/c mice exposed to negative ions for 4 weeks showed no abnormalities in body weight, blood routine analysis, and lung pathology. Our study demonstrates that air ions can be used as a safe and effective means of blocking respiratory virus transmission and contribute to pandemic prevention and control.


Subject(s)
COVID-19 , Influenza A virus , Aerosols , Animals , COVID-19/prevention & control , Cricetinae , Guinea Pigs , Ions , Mice , Pandemics/prevention & control , SARS-CoV-2
14.
Eur Arch Otorhinolaryngol ; 279(9): 4623-4628, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1844363

ABSTRACT

PURPOSE: An association between COVID-19 and olfactory dysfunction has been noted in many patients worldwide. The olfactory adaptation process leads to an increase in intracellular calcium cation levels. Nitrilotriacetic acid trisodium salt has high selective chelation for calcium cations from olfactory mucus. The aim of this work is to test the effect of an intranasal nitrilotriacetic acid trisodium salt to lower the elevated calcium cations in COVID-19 patients with relevant symptoms of olfactory dysfunction. METHODS: Fifty-eight COVID-19 adult patients with relevant symptoms of olfactory dysfunction were enrolled in a prospective randomized controlled trial. They received a nasal spray containing either 0.9% sodium chloride or 2% nitrilotriacetic acid trisodium salt. Olfactory function was assessed before and after treatment using the Sniffin' Sticks test. Quantitative analysis of calcium cation concentration in nasal secretions was performed using a carbon paste ion-selective electrode. RESULTS: After the application of nitrilotriacetic acid trisodium salt compared to sodium chloride, a significant improvement from functional anosmia to healthy normosmia with significant decrease in calcium cation concentration was observed. CONCLUSIONS: Further collaborative research is needed to fully investigate the effect of an intranasal nitrilotriacetic acid trisodium salt in the treatment of olfactory disorders.


Subject(s)
COVID-19 , Olfaction Disorders , Adult , Calcium , Humans , Ions , Nitrilotriacetic Acid , Olfaction Disorders/diagnosis , Olfaction Disorders/drug therapy , Olfaction Disorders/etiology , Prospective Studies , Smell , Sodium Chloride
15.
Mater Horiz ; 9(7): 1935-1946, 2022 07 04.
Article in English | MEDLINE | ID: covidwho-1830192

ABSTRACT

The traditional human-machine interaction mode of communicating solely with pressure sensors needs modification, especially at a time when COVID-19 is circulating globally. Here, a transparent, stretchable, resilient, and high-performance hydrogel fiber-based bimodal sensor is fabricated by using a polyacrylamide-alginate double network hydrogel, which features high sensitivity (3.17% cm-1), wide working range (18 cm), fast response/recovery speeds (90/90 ms) and good stability in proximity sensing, and impressive pressure sensing performance, including high sensitivity (0.91 kPa-1), short response/recovery time (40/40 ms), low detection limit (63 Pa) and good linearity. Moreover, the response switch between proximity/pressure modes is measured and non-interfering dual-mode detection is achieved. Notably, the stretchable bimodal sensor is capable of working under 100% tensile strain without degrading the sensing performance. Specifically, the proximity sensor shows good immunity to the strain, while the pressure sensitivity is even promoted. Furthermore, the sensor is tough enough to work normally after punctures from a knife and strikes from a wrench. Notably, the sensor can be used for gesture recognition and subtle pressure detection, such as small water droplets (10 mg), wrist pulse, etc. A 3 × 3 array is further shown for accurate spatial sensing and location identification, verifying the feasibility of its practical application.


Subject(s)
COVID-19 , Hydrogels , Alginates , Humans , Ions
16.
Medicina (Kaunas) ; 58(4)2022 Mar 23.
Article in English | MEDLINE | ID: covidwho-1810017

ABSTRACT

Background and Objectives: Providing a proper quality control of drugs is essential for efficient treatment of various diseases minimizing the possible side effects of pharmaceutical active substances and potential impurities. Recent in vitro and in vivo studies have shown that certain heavy metalloids and metals interfere with protein folding of nascent proteins in cells and their biological function can be altered. It is unknown whether the drug impurities including heavy metals may affect the tertiary protein structure. Materials and Methods: ReciGen and Rebif are pharmaceutical interferon beta-1a (IFNß-1a) contained in preparations that are used for parenteral administration. Heavy metal impurities of these samples have been studied by gel electrophoresis, Fourier-transform infrared spectroscopy (FTIR) and inductively coupled plasma mass spectrometry analysis (ICP MS). The concentration of heavy metals including mercury, arsenic, nickel, chromium, iron, and aluminum did not exceed permitted levels established by International Council for Harmonisation guideline for elemental impurities. Results: The ICP MS analysis revealed the presence of heavy metals, moreover zeta potential was significantly different for IFNß-1a, which can be an indirect indication of the difference in composition of ReciGen and Rebif samples, respectively. FTIR analysis revealed very similar amide I and II bonds at 1654 and 1560 cm-1 attributed to the peptide absorption peaks of IFNß-1a in Rebif and ReciGen. Conclusions: It was hypothesized that the IFNß-1a complex binds heavy metals affecting the tertiary protein structure and may lead to some side effects of drug administration. Further testing of IFNß-1a bioequivalence for parenteral application is necessary.


Subject(s)
Interferon-beta , Metals, Heavy , Humans , Interferon beta-1a , Interferon-beta/therapeutic use , Ions , Metals, Heavy/toxicity , Pharmaceutical Preparations
17.
Radiat Res ; 198(1): 68-80, 2022 07 01.
Article in English | MEDLINE | ID: covidwho-1793416

ABSTRACT

Here we show an interplay between the structures present in ionization tracks and nucleocapsid RNA structural biology, using fast ion-beam inactivation of the severe acute respiratory syndrome coronavirus (SARS-CoV) virion as an example. This interplay could be a key factor in predicting dose-inactivation curves for high-energy ion-beam inactivation of virions. We also investigate the adaptation of well-established cross-section data derived from radiation interactions with water to the interactions involving the components of a virion, going beyond the density-scaling approximation developed previously. We conclude that solving one of the grand challenges of structural biology - the determination of RNA tertiary/quaternary structure - is linked to predicting ion-beam inactivation of viruses and that the two problems can be mutually informative. Indeed, our simulations show that fast ion beams have a key role to play in elucidating RNA tertiary/quaternary structure.


Subject(s)
Nucleic Acid Conformation , RNA, Viral/chemistry , SARS-CoV-2 , Virus Inactivation , Ions , Models, Molecular , RNA, Viral/metabolism , Radiobiology/methods , SARS-CoV-2/chemistry , Viral Proteins/chemistry , Viral Proteins/metabolism , Virion/chemistry
18.
Nat Biomed Eng ; 6(3): 223-224, 2022 03.
Article in English | MEDLINE | ID: covidwho-1783983
19.
J Am Chem Soc ; 144(15): 6839-6850, 2022 04 20.
Article in English | MEDLINE | ID: covidwho-1773923

ABSTRACT

The envelope (E) protein of the SARS-CoV-2 virus is a membrane-bound viroporin that conducts cations across the endoplasmic reticulum Golgi intermediate compartment (ERGIC) membrane of the host cell to cause virus pathogenicity. The structure of the closed state of the E transmembrane (TM) domain, ETM, was recently determined using solid-state NMR spectroscopy. However, how the channel pore opens to mediate cation transport is unclear. Here, we use 13C and 19F solid-state NMR spectroscopy to investigate the conformation and dynamics of ETM at acidic pH and in the presence of calcium ions, which mimic the ERGIC and lysosomal environment experienced by the E protein in the cell. Acidic pH and calcium ions increased the conformational disorder of the N- and C-terminal residues and also increased the water accessibility of the protein, indicating that the pore lumen has become more spacious. ETM contains three regularly spaced phenylalanine (Phe) residues in the center of the peptide. 19F NMR spectra of para-fluorinated Phe20 and Phe26 indicate that both residues exhibit two sidechain conformations, which coexist within each channel. These two Phe conformations differ in their water accessibility, lipid contact, and dynamics. Channel opening by acidic pH and Ca2+ increases the population of the dynamic lipid-facing conformation. These results suggest an intricate aromatic network that regulates the opening of the ETM channel pore. This aromatic network may be a target for E inhibitors against SARS-CoV-2 and related coronaviruses.


Subject(s)
COVID-19 , Calcium , Calcium/metabolism , Humans , Hydrogen-Ion Concentration , Ions , Lipids , Protein Conformation , SARS-CoV-2 , Water
20.
Cells ; 11(6)2022 03 08.
Article in English | MEDLINE | ID: covidwho-1760407

ABSTRACT

A distinct set of channels and transporters regulates the ion fluxes across the lysosomal membrane. Malfunctioning of these transport proteins and the resulting ionic imbalance is involved in various human diseases, such as lysosomal storage disorders, cancer, as well as metabolic and neurodegenerative diseases. As a consequence, these proteins have stimulated strong interest for their suitability as possible drug targets. A detailed functional characterization of many lysosomal channels and transporters is lacking, mainly due to technical difficulties in applying the standard patch-clamp technique to these small intracellular compartments. In this review, we focus on current methods used to unravel the functional properties of lysosomal ion channels and transporters, stressing their advantages and disadvantages and evaluating their fields of applicability.


Subject(s)
Ion Channels , Lysosomal Storage Diseases , Humans , Intracellular Membranes/metabolism , Ion Channels/metabolism , Ions/metabolism , Lysosomal Storage Diseases/metabolism , Lysosomes/metabolism , Patch-Clamp Techniques
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