Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is ...available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681–686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs may interact SARS-CoV-2 SGPs to facilitate host cell entry. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 SGP bind more tightly to immobilized heparin (KD = 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC50 of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 μM, 0.12 μM, and 26.4 μM, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453–459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. The current study serves a foundation to further investigate biological roles of GAGs in SARS-CoV-2 pathogenesis. Furthermore, our findings may provide additional basis for further heparin-based interventions for COVID-19 patients exhibiting thrombotic complications.
•SARS-CoV-2 spike glycoprotein binds heparin at picomolar binding affinity.•IC50 of heparin against heparin and SARS-CoV-2 spike is in the nanomolar range.•Unbiased docking study reveals potential heparin binding sites on SARS-CoV-2 spike.
In this present review, the current status of the intrinsic mechanical properties of the graphene-family of materials along with the preparation and properties of bulk graphene-based nanocomposites ...is thoroughly examined. The usefulness of Raman spectroscopy for the characterization and study of the mechanical properties of graphene flakes and their composites is clearly exhibited. Furthermore, the preparation strategies of bulk graphene-based nanocomposites are discussed and the mechanical properties of nanocomposites reported in the literature are analysed. In particular, through the analyse of several hundred literature papers on graphene composites, we have found a unique correlation between the filler modulus, derived from the rule of mixtures, and the composite matrix. This correlation is found to hold true across a wide range of polymer matrices and thus suggests that the common assumption that the filler modulus is independent of the matric is incorrect, explaining the apparent under performance of graphene in some systems. The presence of graphene even at very low loadings can provide significant reinforcement to the final material, while the parameters that affect the nanocomposite strongly are thoroughly reviewed. Finally, the potential applications and future perspectives are discussed with regard to scale up capabilities and possible developments of graphene-based nanocomposite materials.
Conventional chemical oxidation routes for the production of graphene oxide (GO), such as the Hummers’ method, suffer from environmental and safety issues due to their use of hazardous and explosive ...chemicals. These issues are addressed by electrochemical oxidation methods, but such approaches typically have a low yield due to inhomogeneous oxidation. Herein we report a two-step electrochemical intercalation and oxidation approach to produce GO on the large laboratory scale (tens of grams) comprising (1) forming a stage 1 graphite intercalation compound (GIC) in concentrated sulfuric acid and (2) oxidizing and exfoliating the stage 1 GIC in an aqueous solution of 0.1 M ammonium sulfate. This two-step approach leads to GO with a high yield (>70 wt %), good quality (>90%, monolayer), and reasonable oxygen content (17.7 at. %). Moreover, the as-produced GO can be subsequently deeply reduced (3.2 at. % oxygen; C/O ratio 30.2) to yield highly conductive (54 600 S m–1) reduced GO. Electrochemical capacitors based on the reduced GO showed an ultrahigh rate capability of up to 10 V s–1 due to this high conductivity.
Polymer nanocomposites reinforced with carbon-based nanofillers are gaining increasing interest for a number of applications due to their excellent properties. The understanding of the reinforcing ...mechanisms is, therefore, very important for the maximization of performance. This present review summarizes the current literature status on the mechanical properties of composites reinforced with graphene-related materials (GRMs) and carbon nanotubes (CNTs) and identifies the parameters that clearly affect the mechanical properties of the final materials. It is also shown how Raman spectroscopy can be utilized for the understanding of the stress transfer efficiency from the matrix to the reinforcement and it can even be used to map stress and strain in graphene. Importantly, it is demonstrated clearly that continuum micromechanics that was initially developed for fibre-reinforced composites is still applicable at the nanoscale for both GRMs and CNTs. Finally, current problems and future perspectives are discussed.
Edible unclonable functions Leem, Jung Woo; Kim, Min Seok; Choi, Seung Ho ...
Nature communications,
01/2020, Volume:
11, Issue:
1
Journal Article
Peer reviewed
Open access
Counterfeit medicines are a fundamental security problem. Counterfeiting medication poses a tremendous threat to patient safety, public health, and the economy in developed and less developed ...countries. Current solutions are often vulnerable due to the limited security levels. We propose that the highest protection against counterfeit medicines would be a combination of a physically unclonable function (PUF) with on-dose authentication. A PUF can provide a digital fingerprint with multiple pairs of input challenges and output responses. On-dose authentication can verify every individual pill without removing the identification tag. Here, we report on-dose PUFs that can be directly attached onto the surface of medicines, be swallowed, and digested. Fluorescent proteins and silk proteins serve as edible photonic biomaterials and the photoluminescent properties provide parametric support of challenge-response pairs. Such edible cryptographic primitives can play an important role in pharmaceutical anti-counterfeiting and other security applications requiring immediate destruction or vanishing features.
The practices and tactics employed in successful optimizations are examined, judged from the trajectories of ligand efficiency and property evolution. A wide range of targets is analyzed, ...encompassing a variety of hit finding methods (HTS, fragments, encoded library technology) and types of molecules, including those beyond the rule of five. The wider employment of efficiency metrics and lipophilicity control is evident in contemporary practice and the impact on quality demonstrable. What is clear is that while targets are different, successful molecules are almost invariably among the most efficient for their target, even at the extremes. Trajectory mapping, based on principles rather than rules, is useful in assessing quality and progress in optimizations while benchmarking against competitors and assessing property-dependent risks.
Abstract
Global models of tide, storm surge, and wave setup are used to obtain projections of episodic coastal flooding over the coming century. The models are extensively validated against tide ...gauge data and the impact of uncertainties and assumptions on projections estimated in detail. Global “hotspots” where there is projected to be a significant change in episodic flooding by the end of the century are identified and found to be mostly concentrated in north western Europe and Asia. Results show that for the case of, no coastal protection or adaptation, and a mean RCP8.5 scenario, there will be an increase of 48% of the world’s land area, 52% of the global population and 46% of global assets at risk of flooding by 2100. A total of 68% of the global coastal area flooded will be caused by tide and storm events with 32% due to projected regional sea level rise.
Composite materials with carbon nanotube and graphene additives have long been considered as exciting prospects among nanotechnology applications. However, after nearly two decades of work in the ...area, questions remain about the practical impact of nanotube and graphene composites. This uncertainty stems from factors that include poor load transfer, interfacial engineering, dispersion, and viscosity-related issues that lead to processing challenges in such nanocomposites. Moreover, there has been little effort to identify selection rules for the use of nanotubes or graphene in composite matrices for specific applications. This review is a critical look at the status of composites for developing high-strength, low-density, high-conductivity materials with nanotubes or graphene. An outlook of the different approaches that can lead to practically useful nanotube and graphene composites is presented, pointing out the challenges and opportunities that exist in the field.
The preparation and characterisation of the different forms of graphene are reviewed first of all. The different techniques that have been employed to prepare graphene such as mechanical and solution ...exfoliation, and chemical vapour deposition are discussed briefly. Methods of production of graphene oxide by the chemical oxidation of graphite are then described. The structure and mechanical properties of both graphene and graphene oxide are reviewed and it is shown that although graphene possesses superior mechanical properties, they both have high levels of stiffness and strength. It is demonstrated how Raman spectroscopy can be used to characterise the different forms of graphene and also follow the deformation of exfoliated graphene, with different numbers of layers, in model composite systems. It is shown that continuum mechanics can be employed to analyse the behaviour of these model composites and used to predict the minimum flake dimensions and optimum number of layers for good reinforcement. The preparation of bulk nanocomposites based upon graphene and graphene oxide is described finally and the properties of these materials reviewed. It is shown that good reinforcement is only found at relatively low levels of graphene loading and that, due to difficulties with obtaining good dispersions, challenges still remain in obtaining good mechanical properties for high volume fractions of reinforcement.
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