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981.
Emily E. F. Brown Reza Rezaei Taylor R. Jamieson Jaahnavi Dave Nikolas T. Martin Ragunath Singaravelu Mathieu J. F. Crupi Stephen Boulton Sarah Tucker Jessie Duong Joanna Poutou Adrian Pelin Hamed Yasavoli-Sharahi Zaid Taha Rozanne Arulanandam Abera Surendran Mina Ghahremani Bradley Austin Chantal Matar Jean-Simon Diallo John C. Bell Carolina S. Ilkow Taha Azad 《International journal of molecular sciences》2021,22(5)
Despite sequence similarity to SARS-CoV-1, SARS-CoV-2 has demonstrated greater widespread virulence and unique challenges to researchers aiming to study its pathogenicity in humans. The interaction of the viral receptor binding domain (RBD) with its main host cell receptor, angiotensin-converting enzyme 2 (ACE2), has emerged as a critical focal point for the development of anti-viral therapeutics and vaccines. In this study, we selectively identify and characterize the impact of mutating certain amino acid residues in the RBD of SARS-CoV-2 and in ACE2, by utilizing our recently developed NanoBiT technology-based biosensor as well as pseudotyped-virus infectivity assays. Specifically, we examine the mutational effects on RBD-ACE2 binding ability, efficacy of competitive inhibitors, as well as neutralizing antibody activity. We also look at the implications the mutations may have on virus transmissibility, host susceptibility, and the virus transmission path to humans. These critical determinants of virus–host interactions may provide more effective targets for ongoing vaccines, drug development, and potentially pave the way for determining the genetic variation underlying disease severity. 相似文献
982.
Hamed Aghamohammadi Akbar Heidarpour 《International Journal of Applied Ceramic Technology》2021,18(4):1192-1204
The effects of hydrofluoric acid (HF) etching time on the morphology of the titanium carbide (TiC) particles with different stoichiometries were investigated. TiC particles with two C/Ti molar ratios of 0.5 and 1.0 were prepared by mechanical alloying. Then, the powders were immersed in the HF solution for different times of 48, 96, and 142 h. Results showed that the morphology of TiC particles greatly changed after HF etching. In general, a roughing phenomenon was observed as a function of the immersion time in the HF solution. The irregular shape of the TiC particles changed to the spherical shapes by increasing the HF etching time. However, the changing tendency of TiC particles with different stoichiometries was different. The shape of prepared powders with a C/Ti molar ratio of 1.0 was polyhedron at the initial stages of HF treatment, while the shape of prepared powders with a C/Ti molar ratio of 0.5 was near-spherical. However, with increasing the immersion time, the shape of both samples changed to a spherical one. The degree of roughing phenomenon of the prepared powders with a C/Ti molar ratio of 0.5 was lower than that of the prepared powders with a C/Ti molar ratio of 1.0. 相似文献
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984.
Dr. Kai S. Yang Xinyu R. Ma Dr. Yuying Ma Dr. Yugendar R. Alugubelli Danielle A. Scott Erol C. Vatansever Aleksandra K. Drelich Dr. Banumathi Sankaran Zhi Z. Geng Lauren R. Blankenship Hannah E. Ward Yan J. Sheng Jason C. Hsu Kaci C. Kratch Dr. Baoyu Zhao Hamed S. Hayatshahi Jin Liu Prof. Pingwei Li Prof. Carol A. Fierke Prof. Chien-Te K. Tseng Prof. Shiqing Xu Prof. Wenshe Ray Liu 《ChemMedChem》2021,16(6):942-948
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2MPro) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus from replicating in infected cells and therefore provides a potential COVID-19 treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 main protease (SC1MPro), we have designed and synthesized a series of SC2MPro inhibitors that contain β-(S-2-oxopyrrolidin-3-yl)-alaninal (Opal) for the formation of a reversible covalent bond with the SC2MPro active-site cysteine C145. All inhibitors display high potency with Ki values at or below 100 nM. The most potent compound, MPI3, has as a Ki value of 8.3 nM. Crystallographic analyses of SC2MPro bound to seven inhibitors indicated both formation of a covalent bond with C145 and structural rearrangement from the apoenzyme to accommodate the inhibitors. Virus inhibition assays revealed that several inhibitors have high potency in inhibiting the SARS-CoV-2-induced cytopathogenic effect in both Vero E6 and A549/ACE2 cells. Two inhibitors, MPI5 and MPI8, completely prevented the SARS-CoV-2-induced cytopathogenic effect in Vero E6 cells at 2.5–5 μM and A549/ACE2 cells at 0.16–0.31 μM. Their virus inhibition potency is much higher than that of some existing molecules that are under preclinical and clinical investigations for the treatment of COVID-19. Our study indicates that there is a large chemical space that needs to be explored for the development of SC2MPro inhibitors with ultra-high antiviral potency. 相似文献
985.
Efforts have been focused on developing an interrelationship between machine direction orientation (MDO)/material variables and the porosity of Al2O3 particulate-filled orientable PP for various applications. Composite films were prepared by cast-extrusion followed by stretching up to 100% and 200% by the MDO machine. Cavitation could occur during film stretching when the adhesion between dispersed alumina and continuous polypropylene phase failed. Composite films with modified micro-particles and also nano ones could not generate any voids. On the other hand, composite specimens of unmodified micro-alumina particles generated micro-pores in the joint between dispersed particles and polymer during the hot stretching. Beta nucleation in these films, plays an important role in the generated ductility of the specimens. Cavitation effectiveness (no. of voids) or film permeability depended on the size and amount of alumina particles, in addition to the ratio and temperature of stretching. Cavitation particles with a size range of 0.7–3 μm, create cavities of about 3–7 μm. Generation of voids, by drawing environmentally friendly and antimicrobial active alumina particles, can be utilized in the fabrication of sustainable hygiene polypropylene films with desirable separation abilities for gases or small molecules. Furthermore, the polypropylene/alumina composite films have the potential for microwaveable packaging. 相似文献
986.
Novel nanosized designed ceramic powders, cerium (Ce) doped bioglass (BG) with various doped Ce content, were synthesized by sol–gel method in order to be employed in the development of PCL fibrous scaffold for bone tissue engineering applications. Characterization techniques such as X-ray diffraction analysis, transmission electron microscopy, Fourier transform infrared spectroscopy, and energy-dispersive X-ray spectroscopy were employed to evaluate the developed Ce doped BG powders. The results confirmed successful doping of Ce inside BG structure. 0, 1, 3, and 10 wt% Ce doped 58S BG were successfully encapsulated in the collagen microspheres by water-in-oil emulsion method and the average particle size and hydrodynamic diameter of microspheres were determined using scanning electron microscopy and dynamic light scattering analysis, respectively. Next, 0, 1, 3, and 10 wt% Ce doped 58S BG encapsulated collagen microspheres were loaded inside the Poly(ɛ-caprolactone) fibrous scaffold and their in vitro bioactivity and biocompatibility properties were evaluated. The results of soaking samples in the simulated body fluid showed that all Ce doped 58S BG encapsulated collagen microspheres loaded PCL fibrous scaffold have acceptable bioactivity and apatite formation ability over time. The biocompatibility evaluation of developed scaffolds showed high viability and proliferation of MG63 cells cultured on the surface of 3% Ce doped 58S BG encapsulated collagen microsphere loaded in the PCL fibrous scaffold and its high potential ability for bone tissue engineering applications. These results potentially open new aspects for scaffolds aimed at the regeneration of bone defects. 相似文献
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990.
Imen Hamed 《Comprehensive Reviews in Food Science and Food Safety》2016,15(6):1104-1123
Microalgal biotechnology has emerged due to the health‐promoting properties of microalgae related to their bioactive compounds and the great diversity of products that can be developed from algal biomass. Microalgal biomasses have been produced industrially for applications in different fields such as food, pharmaceutical, nutraceutical, cosmetic, and animal feed industries. They can be cultivated either in open systems or in closed systems (photobioreactors). Another important area is the use of microalgal biomass for energy production. It has become obvious that petroleum‐derived fuels are unsustainable, due to depleting world reserves and greenhouse gas emissions. Microalgae can provide several different types of renewable biofuels. These include methane produced by anaerobic digestion of the algal biomass, biodiesel derived from trans‐esterification of microalgal lipids, bioethanol produced from carbohydrate fermentations, and photobiologically produced biohydrogen. The idea of using microalgae as a source of fuel is not new. However, it is now being taken seriously because of increases in petroleum prices and, more significantly, the increasing concern about global warming as associated with burning fossil fuels. This review offers an update on information about microalgae, specifically emphasizing their biotechnological importance. 相似文献