Search

This work explores the study of a synthesized nickel complex as a possible inhibitor against the main protease (Mpro) of the recent emerging coronavirus disease (COVID-19). Overall, the template reaction of 3-acetyl-2-hydroxy-6-methyl-4 H -pyran-4-one with nickel(II) chloride hexahydrate in N,N -dimethylformamide (DMF) medium leads to the formation of neutral nickel complex. This resulting complex is formulated as [Ni(DHA) 2 (DMF) 2 ] on the basis of FT-IR, UV-Vis., single-crystal X-ray diffraction analysis, magnetic susceptibility and CV measurements as well as DFT quantum chemical calculations. Its single crystal suggests was found to be surrounded by the both pairs of molecules of DHA and DMF through six oxygen atoms with octahedral coordination sphere. The obtained magnetic susceptibilities are positive and agree with its paramagnetic state. In addition to the experimental investigations, optimized geometry, spectroscopic and electronic properties were also performed using DFT calculation with B3LYP/6-31G(d,p) level of theory. The nonlinear optical (NLO) properties of this complex are again examined. Some suitable quantum descriptors (E HOMO , E LUMO , Energy gap, Global hardness), Milliken atomic charge, Electrophilic potion and Molecular Electrostatic Potential) have been elegantly described. Molecular docking results demonstrated that the docked nickel complex displayed remarkable binding energy with Mpro. Besides, important molecular properties and ADME pharmacokinetic profiles of possible Mpro inhibitors were assessed by in silico prediction., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier B.V. All rights reserved.)

The B.1.617.2 Delta variant is considered to be the most infectious of all SARS-CoV2 variants. Here, an attempt has been made through in-silico screening of 55 bioactive compounds from two selected plants, Saussurea costus and Saussurea involucrata as potential inhibitors of two viral proteases, main protease Mpro (PDB ID:6LU7) and the RBD of SGP of Sars-CoV-2 B1.617.2 Delta variant (PDB ID:7ORB) where the binding energy, molecular interactions, ADMET/Tox, chemical descriptors and Quantum-Chemical Calculations were explored. Molecular docking results demonstrated that the three top docked compounds formed relatively stable complexes within the active site and displayed remarkable binding energy in the order of Tangshenoside III, Rutin and Hesperidin (-9.35, -9.14 and -8.57 kcal/mol, respectively) with Mpro and Rutin, Tangshenoside III and Hesperidin (-9.07, -7.71 and -7.57 kcal/mol) with RBD of SGP. These compounds are non-Mutagen and non-carcinogen. Therefore, according to the Lipinski's Rule of Five they exhibited three violations concerning hydrogen acceptor, donor and molecular weight. However, based on the Quantum-Chemical Calculations results the selected ligands have effective reactivity, as they showed lower band gaps . The difference of the E LUMO and E HOMO was low, ranging from 0.0639 to 0.0978 a.u, implying the strong affinity of these inhibitors towards the target proteins. Among the three inhibitors, Rutin exhibited higher reactivity against two viral proteases, main protease (Mpro) and the Sars-CoV-2 B1.617.2, as the band energy gap was lowest among all the three phytochemicals, 0.0639 a.u This could indicate that Rutincan be potential anti-viral drug candidates against the existing SARS-CoV-2, the B.1.617.2 Delta variant., Competing Interests: The authors declare that they have no known competing finan- cial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier B.V. All rights reserved.)

Objective: Conventional phototherapy converts unconjugated bilirubin to its oxidation products and consequently causes oxidative stress with lipid peroxidation products. New devices that deliver intensive phototherapy are efficacious in treating severe hyperbilirubinemia and minimizing the need for exchange transfusions. However, the oxidative stress status when using these devices has not been explored. Therefore, we aimed to study the impact of using intensive phototherapy on the oxidant-antioxidant status in severely jaundiced neonates., Study Design: This prospective case-control study included term newborns admitted with severe hyperbilirubinemia managed with intensive phototherapy. Baseline oxidant-antioxidant concentrations were compared to healthy controls and re-measured after 8 h of intensive phototherapy exposure., Results: The study included 40 cases with severe jaundice and 40 non-jaundiced apparently normal controls. Total serum bilirubin at enrollment was 23.4 ± 4.2 mg/dl that significantly decreased after 8 h of therapy to 15.4 ± 3.4 mg/dl (p < 0.001). The decline of total serum bilirubin was 1 mg/dl/h. Bilirubin: albumin ratio decreased from 3.45 ± 0.28 to 2.7 ± 0.21 (p < 0.001). Total antioxidant capacity (TAC), superoxide dismutase (SOD), malondialdehyde (MDA), and total oxidative stress (TOS) concentrations were lower in cases (p < 0.001, p < 0.001, p = 0.049, and p < 0.001 respectively) compared to controls. Following 8 h of intensive phototherapy, further decline of TAC (p = 0.016) with increased concentrations of TOS (p = 0.005) were noted. SOD and MDA did not change., Conclusions: Although efficacious, intensive phototherapy was associated with increased oxidative stress. The clinical correlates for harms related to such oxidative stress need further studying., (Copyright © 2021 Elsevier B.V. All rights reserved.)