Effect of Sodium Gluconate on Decreasing Elevated Nasal Calcium and Improving Olfactory Function Post COVID-19 Infection.

BACKGROUND: COVID-19 has been associated with temporary olfactory dysfunction in many infected patients. Calcium plays a great role in the olfaction process with negative feedback for the olfaction transmission. Many reports demonstrated calcium elevation in the nasal secretions with a negative effect on olfaction. Sodium gluconate is a water-soluble salt with a chemical structure that lends to act as a highly efficient chelating agent. It can bind the elevated calcium in the nasal secretions reducing the adverse effects on olfactory function. OBJECTIVE: To evaluate the impact of intranasal sodium gluconate on decreasing the rise of nasal calcium and improving the sense of smell in patients with olfactory dysfunction post-COVID-19 infection. METHODS: Fifty patients with a history of confirmed COVID-19 suffering from olfactory dysfunction persisted more than 90 days after severe acute respiratory syndrome-coronavirus-2 negative testing were included in a prospective randomized blinded controlled clinical trial. Patients were divided into 2 equal groups, receiving either 0.9% sodium chloride or 1% sodium gluconate. Olfactory function was assessed before treatment and 1 month later using the Sniffin' Sticks test. Quantitative analysis of the nasal calcium concentration was performed before treatment and 1 month later using a laboratory-designed screen-printed ion-selective electrode. RESULTS: After using sodium gluconate, the measured olfactory scores indicated a clinical improvement from anosmia to hyposmia compared to the nonimprovement sodium chloride receiving group. Also, a remarked decrease in the calcium nasal concentration was observed after using sodium gluconate compared to sodium chloride. CONCLUSION: Based on the proposed results, sodium gluconate may associate with an improvement of the olfactory dysfunction post-COVID-19 infection.

Fabrication, DFT Calculation, and Molecular Docking of Two Fe(III) Imine Chelates as Anti-COVID-19 and Pharmaceutical Drug Candidate.

Two tetradentate dibasic chelating Schiff base iron (III) chelates were prepared from the reaction of 2,2'-((1E,1'E)-(1,2-phenylenebis(azanylylidene))bis(methanylylidene))bis(4-bromophenol) (PDBS) and 2,2'-((1E,1'E)-((4-chloro-1,2-phenylene)bis(azanylylidene))-bis(methanylylidene))bis(4-bromophenol) (CPBS) with Fe3+ ions. The prepared complexes were fully characterized with spectral and physicochemical tools such as IR, NMR, CHN analysis, TGA, UV-visible spectra, and magnetic moment measurements. Moreover, geometry optimizations for the synthesized ligands and complexes were conducted using the Gaussian09 program through the DFT approach, to find the best structures and key parameters. The prepared compounds were tested as antimicrobial agents against selected strains of bacteria and fungi. The results suggests that the CPBSFe complex has the highest activity, which is close to the reference. An MTT assay was used to screen the newly synthesized compounds against a variety of cell lines, including colon cancer cells, hepatic cellular carcinoma cells, and breast carcinoma cells. The results are expressed by IC50 value, in which the 48 µg/mL value of the CPBSFe complex indicates its success as a potential anticancer agent. The antioxidant behavior of the two imine chelates was studied by DPPH assay. All the tested imine complexes show potent antioxidant activity compared to the standard Vitamin C. Furthermore, the in vitro assay and the mechanism of binding and interaction efficiency of the tested samples with the receptor of COVID-19 core protease viral protein (PDB ID: 6lu7) and the receptor of Gram-negative bacteria (Escherichia coli, PDB ID: 1fj4) were investigated using molecular docking experiments.

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands.

Novel complexes of type [Cu(N-N)(dmtp)2(OH2)](ClO4)2·dmtp ((1) N-N: 2,2'-bipyridine; (2) L: 1,10-phenantroline and dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine) were designed in order to obtain biologically active compounds. Complexes were characterized as mononuclear species that crystallized in the space group P-1 of the triclinic system with a square pyramidal geometry around the copper (II). In addition to the antiproliferative effect on murine melanoma B16 cells, complex (1) exhibited low toxicity on normal BJ cells and did not affect membrane integrity. Complex (2) proved to be a more potent antimicrobial in comparison with (1), but both compounds were more active in comparison with dmtp-both against planktonic cells and biofilms. A stronger antimicrobial and antibiofilm effect was noticed against the Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). Both electron paramagnetic resonance (EPR) and Saccharomyces cerevisiae studies indicated that the complexes were scavengers rather than reactive oxygen species promoters. Their DNA intercalating capacity was evidenced by modifications in both absorption and fluorescence spectra. Furthermore, both complexes exhibited nuclease-like activity, which increased in the presence of hydrogen peroxide.

Zinc as a Drug for Wilson's Disease, Non-Alcoholic Liver Disease and COVID-19-Related Liver Injury.

Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their absorption in the gastrointestinal tract let to introduce zinc in the therapy of Wilson's disease, a congenital disorder of copper metabolism characterized by a systemic copper storage. Nowadays, zinc salts are considered one of the best therapeutic approach in patients affected by Wilson's disease. On the basis of the similarities, at histological level, between Wilson's disease and non-alcoholic liver disease, zinc has been successfully introduced in the therapy of non-alcoholic liver disease, with positive effects both on insulin resistance and oxidative stress. Recently, zinc deficiency has been indicated as a possible factor responsible for the susceptibility of elderly patients to undergo infection by SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Here, we present the data correlating zinc deficiency with the insurgence and progression of Covid-19 with low zinc levels associated with severe disease states. Finally, the relevance of zinc supplementation in aged people at risk for SARS-CoV-2 is underlined, with the aim that the zinc-based drug, classically used in the treatment of copper overload, might be recorded as one of the tools reducing the mortality of COVID-19, particularly in elderly people.

Toxicity-removal efficiency of Brassica juncea, Chrysopogon zizanioides and Pistia stratiotes to decontaminate biomedical ash under non-chelating and chelating conditions: A pilot- scale phytoextraction study.

The healthcare community acknowledged that bio-medical wastes (BMWs) have reached a colossal level across the globe. The recent pandemic (COVID-19) has brought a deluge of contaminated waste which calls for an urgent need of treatment technology for its safe disposal. BMW generally undergoes a conservative treatment approach of incineration which in turn generates potentially toxic ash known as BMW ash. BMW ash, if directly dumped in landfill, leaches and further pollutes both land and groundwater. The present study deployed Brassica juncea [Indian Mustard (IM)], Chrysopogon zizanioides [Vetiver Grass (VG)], and Pistia stratiotes [Water Lettuce (WL)] to remediate toxicity of potentially toxic elements (PTEs) i.e., Cd, Al, Pb, Cu, Mn, Co and Zn in BMW ash both in the presence and absence of chelate with an increased dosage of toxicity. The phyto-assessment results showed that IM extracted 202.2 ± 0.1-365.5 ± 0.02, 7.8 ± 0.03-12.5 ± 0.3, 132.1 ± 0.1-327.3 ± 0.1 and >100 mg kg-1 of Al, Cd, Pb and Zn, respectively without the assistance of a chelating agent. The VG accumulated heavy metals in greater concentration up to 10.5 ± 0.1 and 290.1 ± 0.05 mg kg-1 of Cd and Zn, respectively, and similar trends were observed in the WL set-up. However, the application of an ethylene diamine tetraacetic acid (EDTA) had also increased the efficiency on an average by 20-30% for IM, 35-45% for VG, and 25-35% for WL. The experimental set-up shows that the BCF for IM, VG and WL was found to be greater than 1 for most of the PTEs. The higher value of BCF resulted in a better ability to phytoextract the heavy metals from the soil. The results suggested that IM, VG and WL have the potential to phytoextract PTEs both in the absence and presence of chelating agents.

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator.

Deferoxamine B is an outstanding molecule which has been widely studied in the past decade for its ability to bind iron and many other metal ions. The versatility of this metal chelator makes it suitable for a number of medicinal and analytical applications, from the well-known iron chelation therapy to the most recent use in sensor devices. The three bidentate hydroxamic functional groups of deferoxamine B are the centerpiece of its metal binding ability, which allows the formation of stable complexes with many transition, lanthanoid and actinoid metal ions. In addition to the ferric ion, in fact, more than 20 different metal complexes of deferoxamine b have been characterized in terms of their chemical speciation in solution. In addition, the availability of a terminal amino group, most often not involved in complexation, opens the way to deferoxamine B modification and functionalization. This review aims to collect and summarize the available data concerning the complex-formation equilibria in solutions of deferoxamine B with different metal ions. A general overview of the progress of its applications over the past decade is also discussed, including the treatment of iron overload-associated diseases, its clinical use against cancer and neurodegenerative disorders and its role as a diagnostic tool.

Synthesis of the Bacteriostatic Poly(l-Lactide) by Using Zinc (II)[(acac)(L)H2O] (L = Aminoacid-Based Chelate Ligands) as an Effective ROP Initiator.

The paper presents a synthesis of poly(l-lactide) with bacteriostatic properties. This polymer was obtained by ring-opening polymerization of the lactide initiated by selected low-toxic zinc complexes, Zn[(acac)(L)H2O], where L represents N-(pyridin-4-ylmethylene) tryptophan or N-(2-pyridin-4-ylethylidene) phenylalanine. These complexes were obtained by reaction of Zn[(acac)2 H2O] and Schiff bases, the products of the condensation of amino acids and 4-pyridinecarboxaldehyde. The composition, structure, and geometry of the synthesized complexes were determined by NMR and FTIR spectroscopy, elemental analysis, and molecular modeling. Both complexes showed the geometry of a distorted trigonal bipyramid. The antibacterial and antifungal activities of both complexes were found to be much stronger than those of the primary Schiff bases. The present study showed a higher efficiency of polymerization when initiated by the obtained zinc complexes than when initiated by the zinc(II) acetylacetonate complex. The synthesized polylactide showed antibacterial properties, especially the product obtained by polymerization initiated by a zinc(II) complex with a ligand based on l-phenylalanine. The polylactide showed a particularly strong antimicrobial effect against Pseudomonas aeruginosa, Staphylococcus aureus, and Aspergillus brasiliensis. At the same time, this polymer does not exhibit fibroblast cytotoxicity.

Effectiveness of chelating agent-assisted Fenton-like processes on remediation of glucocorticoid-contaminated soil using chemical and biological assessment: performance comparison of CaO2 and H2O2.

Glucocorticoids (GCs) have drawn great concern due to widespread contamination in the environment and application in treating COVID-19. Most studies on GC removal mainly focused on aquatic environment, while GC behaviors in soil were less mentioned. In this study, degradation of three selected GCs in soil has been investigated using citric acid (CA)-modified Fenton-like processes (H2O2/Fe(III)/CA and CaO2/Fe(III)/CA treatments). The results showed that GCs in soil can be removed by modified Fenton-like processes (removal efficiency gt; 70% for 24 h). CaO2/Fe(III)/CA was more efficient than H2O2/Fe(III)/CA at low oxidant dosage (< 0.28-0.69 mmol/g) for long treatment time (> 4 h). Besides the chemical assessment with GC removal, effects of Fenton-like processes were also evaluated by biological assessments with bacteria and plants. CaO2/Fe(III)/CA was less harmful to the richness and diversity of microorganisms in soil compared to H2O2/Fe(III)/CA. Weaker phytotoxic effects were observed on GC-contaminated soil treated by CaO2/Fe(III)/CA than H2O2/Fe(III)/CA. This study, therefore, recommends CaO2-based treatments to remediate GC-contaminated soils.

Upregulation of the Renin-Angiotensin System Pathways and SARS-CoV-2 Infection: The Rationale for the Administration of Zinc-Chelating Agents in COVID-19 Patients.

The article describes the rationale for the administration of zinc-chelating agents in COVID-19 patients. In a previous work I have highlighted that the binding of the SARS-CoV spike proteins to the zinc-metalloprotease ACE2 has been shown to induce ACE2 shedding by activating the zinc-metalloprotease ADAM17, which ultimately leads to systemic upregulation of ACE2 activity. Moreover, based on experimental models, it was also shown the detrimental effect of the excessive systemic activity of ACE2 through its downstream pathways, which leads to "clinical" manifestations resembling COVID-19. In this regard, strong upregulation of circulating ACE2 activity was recently reported in COVID-19 patients, thus supporting the previous hypothesis that COVID-19 may derive from upregulation of ACE2 activity. Based on this, a reasonable hypothesis of using inhibitors that curb the upregulation of both ACE2 and ADAM17 zinc-metalloprotease activities and consequent positive feedback-loops (initially triggered by SARS-CoV-2 and subsequently sustained independently on viral trigger) is proposed as therapy for COVID-19. In particular, zinc-chelating agents such as citrate and ethylenediaminetetraacetic acid (EDTA) alone or in combination are expected to act in protecting from COVID-19 at different levels thanks to their both anticoagulant properties and inhibitory activity on zinc-metalloproteases. Several arguments are presented in support of this hypothesis and based on the current knowledge of both beneficial/harmful effects and cost/effectiveness, the use of chelating agents in the prevention and therapy of COVID-19 is proposed. In this regard, clinical trials (currently absent) employing citrate/EDTA in COVID-19 are urgently needed in order to shed more light on the efficacy of zinc chelators against SARS-CoV-2 infection in vivo.

EDTA-K2 Improves the Detection Sensitivity of SARS-CoV-2 IgM and IgG Antibodies by Chelating Colloidal Gold in the Immunochromatographic Assay.

OBJECTIVE: The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now rapidly spreading globally. Serological tests are an important method to assist in the diagnosis of COVID-19, used for epidemiological investigations. In this study, we aimed to investigate the impact of different types of vacuum collection tubes on the detection of SARS-CoV-2 IgM and IgG antibodies, using the colloidal gold immunochromatographic assay (GICA). PATIENTS AND METHODS: A total of 112 patients with COVID-19 and 200 healthy control subjects with no infection were enrolled in this study. Their serum and plasma were collected into four different types of vacuum blood collection tubes. SARS-CoV-2 IgM and IgG specific antibodies in the plasma and serum were then detected by GICA and chemiluminescence assay (CA), respectively. In addition, the particle sizes of different colloidal gold solutions in the presence of different anticoagulants and coagulants were evaluated by both laser diffraction (Malvern) and confocal laser microscope, respectively. RESULTS: Our results revealed that anticoagulated plasma with EDTA-K2 improved the positive detection rate of SARS-CoV-2 IgM antibodies. Furthermore, our results shown that the detection results by GICA and CA were highly consistent, especially, the results of EDTA-K2 anticoagulated plasma detected by GICA was more consistent with CA results. We confirmed that EDTA-K2 could improve the detection sensitivity of SARS-CoV-2 IgG antibodies by chelating excessive colloidal gold compared with sodium citrate or lithium heparin, these methodologies did not appear to cause false positives. Colloidal gold particles could be chelated and aggregated by EDTA-K2, but not by sodium citrate, lithium heparin and coagulants. CONCLUSION: GICA is widely used to detect antibodies for the advantages of convenient, fast, low cost, suitable for screening large sample and require minimal equipment. In this study, we found that EDTA-K2 amplified the positive antibody signal by chelating colloidal gold and improved the detection sensitivity of SARS-CoV-2 IgM and IgG antibodies when using the GICA. Therefore, we suggested that EDTA-K2 anticoagulated plasma was more suitable for the detection of SARS-CoV-2 antibodies.

Food-derived antioxidants and COVID-19.

SARS-CoV-2 (previously 2019-nCoV), the pathogenic agent of COVID-19 disease, started to expand from Wuhan, China, on December 2019 and in 2 months, it spread worldwide giving origin to a pandemic. COVID-19 has a stronger transmission capacity by inhalation of infectious aerosols and after an incubation time of 3-14 days, it may be responsible for diseases ranging from the asymptomatic to fatal consequences. COVID-19 has emerged as a multifaceted, multisystem, multi-organ disorder, which produces its pathogenic effects through a quite ubiquitous target at the level of multiple organs and in which oxidative stress and inflammatory process play relevant roles. Thus, besides the development of a pharmacological therapy, in the field of alternative and coadjutant therapeutic, the use of dietary supplements or nutraceuticals for the prevention or treatment of SARS-CoV-2 infection may be a useful strategy. Herein, we specifically comment on some literature evidences, which link the food-derived antioxidants and metal-chelating agents with treatment and prevention of oxidative stress and inflammation that play a key role in the progression of COVID-19. PRACTICAL APPLICATIONS: Oxidative stress and inflammation are key factors increasing COVID-19 severity especially in the presence of chronic diseases associated with the antioxidant system fragility. These evidences support the recommendation of antioxidants supplementation as useful strategies against COVID-19. In light with these observations, herein, a comment which describes the major antioxidants and metal-chelating agents from food sources that might be useful for the treatment and prevention of oxidative stress and inflammation during COVID-19.

The past, present and future of RNA respiratory viruses: influenza and coronaviruses.

Influenza virus and coronaviruses continue to cause pandemics across the globe. We now have a greater understanding of their functions. Unfortunately, the number of drugs in our armory to defend us against them is inadequate. This may require us to think about what mechanisms to address. Here, we review the biological properties of these viruses, their genetic evolution and antiviral therapies that can be used or have been attempted. We will describe several classes of drugs such as serine protease inhibitors, heparin, heparan sulfate receptor inhibitors, chelating agents, immunomodulators and many others. We also briefly describe some of the drug repurposing efforts that have taken place in an effort to rapidly identify molecules to treat patients with COVID-19. While we put a heavy emphasis on the past and present efforts, we also provide some thoughts about what we need to do to prepare for respiratory viral threats in the future.

Arsenic intoxication: general aspects and chelating agents.

Arsenic (As) is widely used in the modern industry, especially in the production of pesticides, herbicides, wood preservatives, and semiconductors. The sources of As such as contaminated water, air, soil, but also food, can cause serious human diseases. The complex mechanism of As toxicity in the human body is associated with the generation of free radicals and the induction of oxidative damage in the cell. One effective strategy in reducing the toxic effects of As is the usage of chelating agents, which provide the formation of inert chelator-metal complexes with their further excretion from the body. This review discusses different aspects of the use of metal chelators, alone or in combination, in the treatment of As poisoning. Consideration is given to the therapeutic effect of thiol chelators such as meso-2,3-dimercaptosuccinic acid, sodium 2,3-dimercapto-1-propanesulfonate, 2,3-dimercaptopropanol, penicillamine, ethylenediaminetetraacetic acid, and other recent agents against As toxicity. The review also considers the possible role of flavonoids, trace elements, and herbal drugs as promising natural chelating and detoxifying agents.