Graphene Oxide Nanosheets Interact and Interfere with SARS‐CoV‐2 Surface Proteins and Cell Receptors to Inhibit Infectivity

From Wiley via Jisc Publications RouterHistory: received 2021-03-13, pub-electronic 2021-05-14Article version: VoRPublication status: PublishedFunder: University of PaduaFunder: UKRI EPSRC; Grant(s): EP/P00119X/1Funder: Turkish Academy of Sciences (TUBA)Funder: Scientific and Technology Council of Turkey; Grant(s): 18AG020Funder: Türkiye Bilimler Akademisi; Id: http://dx.doi.org/10.13039/501100004412; Grant(s): GEBIP 2018Funder: Türkiye Bilimsel ve Teknolojik Araştirma Kurumu; Id: http://dx.doi.org/10.13039/501100004410; Grant(s): 18AG020Funder: Engineering and Physical Sciences Research Council; Id: http://dx.doi.org/10.13039/501100000266; Grant(s): EP/P00119X/1Abstract: Nanotechnology can offer a number of options against coronavirus disease 2019 (COVID‐19) acting both extracellularly and intracellularly to the host cells. Here, the aim is to explore graphene oxide (GO), the most studied 2D nanomaterial in biomedical applications, as a nanoscale platform for interaction with SARS‐CoV‐2. Molecular docking analyses of GO sheets on interaction with three different structures: SARS‐CoV‐2 viral spike (open state – 6VYB or closed state – 6VXX), ACE2 (1R42), and the ACE2‐bound spike complex (6M0J) are performed. GO shows high affinity for the surface of all three structures (6M0J, 6VYB and 6VXX). When binding affinities and involved bonding types are compared, GO interacts more strongly with the spike or ACE2, compared to 6M0J. Infection experiments using infectious viral particles from four different clades as classified by Global Initiative on Sharing all Influenza Data (GISAID), are performed for validation purposes. Thin, biological‐grade GO nanoscale (few hundred nanometers in lateral dimension) sheets are able to significantly reduce copies for three different viral clades. This data has demonstrated that GO sheets have the capacity to interact with SARS‐CoV‐2 surface components and disrupt infectivity even in the presence of any mutations on the viral spike. GO nanosheets are proposed to be further explored as a nanoscale platform for development of antiviral strategies against COVID‐19

Ultrasensitive Determination of Glial-Fibrillary-Acidic-Protein (GFAP) in Human Serum-Matrix with a Label-Free Impedimetric Immunosensor

In this work, immobilizing anti-GFAP antibodies via covalent attachment onto L-cysteine/gold nanoparticles that were modified with screen-printed carbon electrodes (Anti-GFAP/L-cys/AuNps/SPCE) resulted in the development of a sensitive label-free impedance immunosensor for the detection of Glial Fibrillary Acidic Protein (GFAP). The immunosensor’s stepwise construction was studied using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). L-cysteine was chosen as the linker between GFAP antibodies and Au NPs/SPCE because it enables the guided and stable immobilization of GFAP antibodies, thus resulting in increased immunosensor sensitivity. As a redox probe, 5 mM of [Fe(CN)6]3−/4− was used to measure the electron–transfer resistance (Ret), which was raised by the binding of antigens to the immobilized anti-GFAP on the surface of the modified electrode. A linear correlation between Rct and GFAP concentration was achieved under optimum conditions in the range of 1.0–1000.0 pg/mL, with an extraordinarily low detection limit of 51.0 fg/mL. The suggested immunosensor was successfully used to detect the presence of GFAP in human blood serum samples, yielding good findings. As a result, the proposed platform may be utilized to monitor central nervous system injuries

Effect of Disulfide Bonds on the Thermal Stability of Pediocin: In-silico Screening Using Molecular Dynamics Simulation

The thermal stability properties of pediocin at 310, 313, 323, 333, 343, and 348 K (37, 40, 50, 60, 70, and 75°C, respectively) are reported in this study. A theoretical approach, such as the molecular dynamics method, was used to analyze the structure. Molecular dynamics simulation confirms the stability of molecules with Cys. Furthermore, this study reveals that Cys residues play an essential role in structure stability at high temperatures. To understand the structural basis for the stability of pediocin, a detailed in-silico analysis using molecular dynamics simulations to explore the thermal stability profiles of the compounds was conducted. This study shows that thermal effects fundamentally alter the functionally crucial secondary structure of pediocin. However, as previously reported, pediocin’s activity was strictly conserved due to the disulfide bond between Cys residues. These findings reveal, for the first time, the dominant factor behind the thermodynamic stability of pediocin

Neuronavigation-assisted percutaneous balloon compression for the treatment of trigeminal neuralgia: The technique and short-term clinical results.

Background. Percutaneous balloon compression (PBC) has been widely used in the treatment of trigeminal neuralgia. However, this technique has a steep learning curve and significant complications were reported that were related to foramen ovale puncturing. The aim of this study was to evaluate the clinical results of a small patient group who underwent neuronavigation-assisted PBC. Methods. An intraoperative computed tomography (CT) device (CereTom, Neurologica, Danvers, MA/USA) was used to obtain CT scans with 2-mm slice thicknesses. The data were transferred to a neuronavigation system planning station (BrainLab, Feldkirchen, Germany). A soft touch registration system was used for image registration. With the image guidance, a trajectory was defined and the foramen ovale was cannulated using neuronavigation and Hartel's landmarks. Results. Sixteen procedures were performed on 13 patients (4 female and 9 male) without complications. The total length of the procedure was not more than 57 min in all instances. Conclusions. We believe that image-guided neuronavigation is useful for neurosurgeons who are at the beginning of their PBC learning curve. It may also be an alternative for particular patients with significant anatomic variations that result in an unsuccessful foramen ovale puncture

Investigation of pazopanib and human serum albumin interaction using spectroscopic and molecular docking approaches

Abstract Pazopanib (PAZ), a tyrosine kinase inhibitor, is used to treat advanced renal cell carcinoma (RCC) and advanced soft tissue sarcoma (STS). The FDA approved PAZ for RCC in 2009 and for STS in 2012. The antitumor activity of pazopanib, according to the degree of inhibition, shows different results depending on the dose. Renal cell carcinoma is the most sensitive carcinoma to pazopanib, with 77% inhibition at the 10 mg/kg dose. Clinical studies have shown 53% to 65% inhibition in carcinomas such as breast carcinoma, prostate carcinoma, and melanoma. Plasma proteins such as human serum albumin (HSA) have a critical role in transporting and storing bioactive components. This feature of HSA is very important for the development of cancer therapy. Here, we investigated the interaction between PAZ and HSA to evaluate their binding strength, binding types, and conformational change in HSA. We used spectroscopic methods to assess the drug–protein interaction. Fluorescence measurements revealed that the interaction of PAZ with HSA occurred via the static quenching mechanism. The calculated binding number and binding constants were 1.041 and 1.436 × 10⁶ M⁻¹, respectively, at 298.15 K based on fluorescence screening. The high binding constant and calculated Gibbs free energy at different temperatures showed spontaneous and strong binding. Circular dichroism measurements showed that the α-helix structure of HSA was retained as the secondary structure, with a slight reduction in its percentage after adding PAZ. Furthermore, molecular modeling studies suggested that the docking score of PAZ is higher than those of bicalutamide and ibuprofen, the drugs that were chosen as model competitors against PAZ. Accordingly, PAZ was found to replace bicalutamide and ibuprofen on the HSA binding site, which was also confirmed by UV absorption spectroscopy

Unilateral Endoscopic Optic Nerve Decompression for Idiopathic Intracranial Hypertension: A Series of 10 Patients

OBJECTIVE: Several surgical treatment modalities, including lumboperitoneal or ventriculoperitoneal shunt surgery, subtemporal decompression, endovascular venous sinus stenting, optic nerve decompression (OND), were used in the management of idiopathic intracranial hypertension (IIH). Each surgical technique has different advantages and disadvantages. Endoscopic OND is rarely used in the management of IIH. There are only four reported cases. The aim of this study is to describe the surgical results of patients treated with this less invasive surgical technique

Endovascular treatment of posterior circulation aneurysms: Results from a single-team experience of 81 cases including 13 flow diversion treatment.

Introduction:Relatively constant surgical risks and rapid advances in endovascular treatment have caused a major shift toward endovascular management of posterior circulation aneurysms. This paper presents the results of a series of endovascularly treated posterior circulation aneurysms.Methods:A total of 81 patients who underwent endovascular treatment of posterior circulation aneurysms performed by a single team between 2009 and 2019 were included. Demographic, clinical, radiologic, and management details were retrospectively obtained from hospital records.Results:Among the included patients, 50 (61.7%) and 31 (38.3%) were female and male, respectively. Subarachnoid hemorrhage was observed in 30 patients (37%). Moreover, 40 (49.3%) aneurysms were treated with stent-assisted coiling, 1 (1.2%) aneurysm was treated with parent artery occlusion, 2 (2.4%) aneurysms were coiled using balloon assistance, 24 (29.6%) aneurysms were coiled primarily, 1 (1.2%) patient had an unsuccessful treatment attempt, and 13 (16.0%) aneurysms were treated with flow-diverter stents or stent monotherapy. During the last follow-up, 57 (83.8%) aneurysms were completely occluded, whereas 6 (8.8%) and 2 (2.9%) aneurysms did and did not have a residual neck, respectively. Flow diversion was used to treat 13 patients, among whom 8 had total occlusion or stable residue. A total of 7 deaths (8.6%) were encountered in this series.Conclusion:Endovascular treatment should be considered as the primary treatment modality for posterior circulation aneurysms. Despite the high morbidity and mortality rates, promising results can be achieved with correct patient selection. Flow diversion can be a feasible alternative for complex aneurysms that are difficult to treat.Keywords:Aneurisma; Aneurysm; Circulación posterior; Endovascular; Hemorragia subaracnoidea; Posterior circulation; Stent; Subarachnoid hemorrhage