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.
ABSTRACT
Interferons (IFN) have antiviral activity against many viruses, including SARS-CoV-2. A combination of IFN-a2b and the antioxidant taurine is widely used in the Russian Federation, and its antiviral activity has not been studied before. The aim of this study was to determine the antiviral activity of interferon drugs, in combination with taurine and without it. The study included cytotoxicity and antiviral activity assays of IFN-a2b preparations, when stored according to the instructions at 2-8°C, and after 1 month storage at the temperature of 20-26°C in a pre-opened state. The combination of IFN alpha-2b with taurine has a higher antiviral activity compared to IFN alpha-2b mono-preparation by more than 25% at a «low» and 85% at a «high» multiplicity of infection. Selectivity index for combinations of IFN-a2b (50,000 IU/dose) + taurine (1 mg/ml) and IFN-a2b (10,000 IU/ml) + taurine (0.8 mg/ml) was more than 600 units, whereas for the IFN-a2b (10,000 IU/ml) it was 200 units. Antiviral activity does not change after one month at room temperature. The combination of interferon with taurine at high concentrations was less toxic than interferon. The results obtained demonstrate practicability of interferon alpha-2b and taurine combination use for treatment and prevention of COVID-19.
ABSTRACT
High redox potential reactive oxygen and nitrogen species (ROS/RNS), such as O2 free radicals, superoxide, and hypochlorous acid, generated by activities of the NADPH oxidase-2 (NOX2)/myeloperoxidase (MPO) axis and related enzymes, are key effector molecules of innate immunity in physiological and diseased inflammatory states. Other lower energy species (H2O2, NO) provide adjuvant signaling functions. NOX2- and MPO-derived high energy radicals are known to oxidize naphthol species, wherein the naphthol products bind to proximate proteins and activated myeloid cells. Herein, we present 4-[18F]fluoro-1-naphthol ([18F]4FN), a novel redox-tuned radiopharmaceutical that selectively detects by positron emission tomography (PET) high energy radicals produced by activated innate immunity. The products of human MPO plus H2O2 , but not H2O2 alone, rapidly and completely oxidized [18F]4FN. All-trans-retinoic acid-differentiated HL-60 'neutrophil-like' human cells activated with phorbol-12-myristate-13-acetate (PMA) retained [ 18F]4FN 5-fold over unstimulated cells. 4-ABAH, an MPO-specific inhibitor, or DPI, a broad oxidase inhibitor, blocked cellular retention by >95%. [18F]4FN PET/CT imaging readily discriminated foci of inflammation in vivo in three distinct murine models of acute inflammation: endotoxin-induced whole-body toxic shock, PMA-induced mild contact dermatitis of the ear, and lipopolysaccharide (LPS)-induced ankle arthritis. Mechanistically, in mice in vivo, 4-ABAH reduced inflammationinduced [18F]4FN retention, and Cybb-/- (Nox2-/-) gene-deletion strongly and significantly abrogated PMA-induced [18F]4FN retention. Thus, [18F]4FN shows promise as a robust redox-tuned reporter for imaging activation states of innate immunity by PET/CT, is ready for translation. [18F]4FN PET imaging may find application in a variety of inflammatory states associated with cancer therapy, immunotherapy-related adverse events, as well as other diseases, including arthritis, hepatitis, atherosclerosis, COVID-19, as well as up-staging and monitoring multi-organ inflammation.
ABSTRACT
Introduction: The Coronavirus Disease-2019 (COVID-19) pandemic has spread rapidly, infecting more than 194 million and killing more than 4 million people worldwide. Algeria has not escaped this scourge;according to World Health Organization (WHO), 162,155 confirmed cases and 4,063 deaths have been recorded from 3rdJanuary 2020 to 26thJuly 2021. Recent studies have indicated the critical role of an altered immune system, and oxidative stress in the pathological process contributing to several complications during COVID-19 disease. Aim: To determine blood markers, oxidant/antioxidant status and biochemical parameters in patients highly recovered from COVID-19 and compare with those who have never contracted COVID-19;considered as controls. Materials and Methods: The present case-control study was conducted in Tiaret, Algeria, between May 2021 and June 2021. Thirty healthy volunteers who had never contracted COVID-19 and 16 volunteers who recovered from COVID-19 in the last six months were included in the study. Blood samples were taken after 8 to 12 hours of fasting, the blood markers and biochemical parameters were evaluated. The participant with chronic diseases (diabetes, hypertension, cardiovascular diseases, kidney disease) was excluded. Student's t-test was performed for statistical comparison between the two groups. Statistical analysis was performed using Excel Microsoft 2010 software. Results. The control group consisted of 46.7% male (n=14) and 53.3% females (n=16). While, the case group consisted of 62.5% males (n=10) and 37.5% females (n=6). The plasma levels of Low Density Lipoprotein-Cholesterol (LDL-C), p-value=0.004∗∗and creatinine increased very significantly in the cases compared to the controls. While, total cholesterol, p-value=0.04∗and Glutamate Pyruvate Transaminase (GPT), p-value=0.03∗ increased significantly in the case group on comparision to the control group. On the other hand, erythrocyte Malondialdehyde (MDA) levels, p-value=0.009∗∗increased very significantly in the case group compared to controls. The erythrocyte activity catalase decreased highly significantly in the case group compared to the controls. But erythrocyte Reduced glutathione (GSH) decreased very significantly in group cases compared to controls. Conclusion: The findings in the present study confirmed the persistence of metabolic alterations and oxidative stress in COVID-19 patients after recovery. Antioxidant supplementation is recommended to improve redox status and reduce oxidative stress after recovery.
ABSTRACT
Background: In most serious COVID-19 forms which required prolonged stay in intensive care unit, pulmonary, cardiovascular, renal, neurological and psychological sequelae have been reported after the infection. All these complications can be sustained by chronic inflammatory problems and/ or increased oxidative stress. Material and Methods: Biomarkers of the systemic oxidative stress status (OSS) including enzymatic and non-enzymatic antioxidants, total antioxidant capacity of plasma (PAOT®-Sore), trace elements, oxidative damage to lipids and inflammation markers, were investigated in 12 patients admitted to a revalidation center for post-19 COVID pneumonia. Results: From blood samples collected two months after hospital discharge and one month after admission to the revalidation center, vitamin C, thiol proteins, reduced glutathione, gamma-tocopherol and beta carotene were significantly decreased compared to reference values. By contrast, lipid peroxides and markers of inflammation (neutrophils, myeloperoxidase) were significantly higher than the norms. Lipid peroxides was strongly correlated with Cu (r = 0.95, P < 0.005) and Cu/Zn ratio (0.66, P = 0.020). Using an electrochemical method (PAOT®), total antioxidant capacity (TAC) evaluated in saliva and urine negatively correlated with copper and lipid peroxides. Similar findings were obtained for PAOT®-skin score. Conclusions: Systemic OSS was strongly altered in patients admitted in revalidation after C0VID-19 infection. This suggests the need for supplementing these patients with antioxidants.