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Three-dimensional structures of SARS-CoV-2 and other coronaviral proteins archived in the Protein Data Bank were used to analyze viral proteome evolution during the first six months of the COVID-19 pandemic. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48,000 viral proteome sequences showed how each one of the 29 viral study proteins have undergone amino acid changes. Structural models computed for every unique sequence variant revealed that most substitutions map to protein surfaces and boundary layers with a minority affecting hydrophobic cores. Conservative changes were observed more frequently in cores versus boundary layers/surfaces. Active sites and protein-protein interfaces showed modest numbers of substitutions. Energetics calculations showed that the impact of substitutions on the thermodynamic stability of the proteome follows a universal bi-Gaussian distribution. Detailed results are presented for six drug discovery targets and four structural proteins comprising the virion, highlighting substitutions with the potential to impact protein structure, enzyme activity, and functional interfaces. Characterizing the evolution of the virus in three dimensions provides testable insights into viral protein function and should aid in structure-based drug discovery efforts as well as the prospective identification of amino acid substitutions with potential for drug resistance.

This article aims to investigate the low-velocity impact behaviour of non-symmetric FMLs bonded with aluminium sheets and carbon fibre composite laminates by experimental and numerical methods. Two...

The understanding of the composition dependent properties and freezing-thawing (F-T) resistance of geopolymer materials is vital to their applications in cold regions. In this study, metakaolin-based geopolymer (MKG) mortars were fabricated by controlling the Si/Al ratio and the Na/Al ratio. The pore structure and strength were measured by mercury intrusion porosimetry and compression tests, respectively, which both showed obvious correlations with the material composition. Mass loss, strength loss, visual rate, and microscopic observation were adopted to assess the changes of the material properties and microstructure caused by F-T loads. The results showed that the strength-porosity relationship roughly followed a linear plot. Increases of the Si/Al ratio increased the capillary pore volume, but decreased the gel pore volume and the F-T resistance. Increases of the Na/Al ratio decreased the gel pore, but roughly enhanced the F-T resistance. The MKG mortar at the Na/Al ratio of 1.26 showed the lowest total pore volume and the best F-T resistance. The mechanisms of our experimental observations were that the abundantly distributed air voids connected by the capillary pores facilitated the relaxation of hydraulic pressures induced by the freezing of the pore liquid. The findings of this work help better clarify the compositional dependence of the pore structure, strength, and freezing-thawing resistance of MKG materials and provide fundamental bases for their engineering applications in cold regions.

To date, great efforts have been made to prepare different kinds of isotropic tissue engineering (TE) scaffolds. However, little attention has been paid to anisotropic porous scaffolds in spite of many examples of their excellent performances. In this work, a facile method termed "ammonia-induced method" (AIM) was proposed and applied to generate anisotropic pores in chitosan (CS)-based scaffolds. The pore structures of these scaffolds were studied in detail. In order to clarify the rationale behind this process, a speculative explanation was provided on basis of the experimental results and the theory of Uras (Uras & Devlin, 2000). Compression tests indicated that the mechanical strengths of these scaffolds were sufficient for TE applications. In vitro cell culture showed that MC3T3-E1 cells cultivated in the pores of these scaffolds had positive proliferation potential. We anticipated that this novel AIM could inspire research not only in TE but also in other fields.

To explore the correlating thermodynamic factors to the structural aspects that account for the stability of the RNA triplex, two functional Ru(II) complexes containing the same ancillary ligands and different intercalative ligands, [Ru(bpy)(2)(mip)](2+) (bpy=2,2'-bipyridine, mip=2'-(3",4"-methylene-dioxyphenyl)imidazo[4',5'-f][1,10]phenanthroline) and [Ru(bpy)(2)(bdip)](2+) (bdip=2-(1,3-benzodioxol-4-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) have been synthesized. The binding properties of [Ru(bpy)(2)(mip)](2+) and [Ru(bpy)(2)(bdip)](2+) to the RNA triplex poly(U)•poly(A)*poly(U) have been investigated by various biophysical techniques and quantum chemistry calculations. Compared with [Ru(bpy)(2)(bdip)](2+), remarkably higher binding and stabilization of the triplex RNA structure by [Ru(bpy)(2)(mip)](2+) is achieved upon changing the substituent positions on the intercalative ligand. The result reveals that the intercalative ligand shape plays a critical role in third-strand stabilization.

The binding properties of [RuL(2)(mip)](2+) {where L is 1,10-phenanthroline (phen) or 4,7-dimethyl-1,10-phenanthrollne (4,7-dmp) and mip is 2'-(3",4"-methylenedioxyphenyl)imidazo[4',5'-f][1,10]phenanthroline} with regard to the triplex RNA poly(U)·poly(A)*poly(U) were investigated using various biophysical techniques and quantum chemistry calculations. In comparison with [Ru(4,7-dmp)(2)(mip)](2+), remarkably higher binding affinity of [Ru(phen)(2)(mip)](2+) for the triplex RNA poly(U)·poly(A)*poly(U) was achieved by changing the ancillary ligands. The stabilization of the Hoogsteen-base-paired third strand was improved by about 10.9 °C by [Ru(phen)(2)(mip)](2+) against 6.6 °C by [Ru(4,7-dmp)(2)(mip)](2+). To the best of our knowledge, [Ru(phen)(2)(mip)](2+) is the first metal complex able to raise the third-strand stabilization of poly(U)·poly(A)*poly(U) from 37.5 to 48.4 °C. The results reveal that the ancillary ligands have an important effect on third-strand stabilization of the triplex RNA poly(U)·poly(A)*poly(U) when metal complexes contain the same intercalative ligands.

Two new Ru(II) complexes with 1,8-naphthalimide group, [Ru(phen)2(pnip)](2+) (Ru1; phen=1,10-phenanthroline, pnip=2-[N-(p-phenyl)-1,8-napthalimide]imidazo[4',5'-f][1,10]phenanthroline) and [Ru(bpy)2(pnip)](2+) (Ru2; bpy=2,2'-bipyridine), have been synthesized and characterized. The interactions of Ru1 and Ru2 with the triplex RNA poly(U)•poly(A)*poly(U) (where • denotes the Watson-Crick base pairing and * denotes the Hoogsteen base pairing) were studied by various biophysical. Electronic spectra established that the binding affinity for Ru1 was greater than that for Ru2. Fluorescence and viscosity studies gave convincing evidence for a true intercalative binding of both complexes with the RNA triplex. UV melting studies confirmed that the two complexes could stabilize the triplex, whereas the effects of the two complexes on the stability of the Hoogsteen base-paired strand ploy(U) and the Watson-Crick base-paired duplex poly(U)•poly(A) of the triplex were different. In the case of Ru1, the increase of the thermal stability of the Hoogsteen base-paired strand was stronger than that of the Watson-Crick base-paired duplex. However, an opposite effect was observed in the case of Ru2. Circular dichroic studies suggested that the RNA triplex undergoes a conformational transition in the presence of Ru1, whereas the helicity of the RNA triplex still remains A-type in the presence of Ru2. The main results obtained here further advance our knowledge on the interaction of RNA triple-stranded structures with metal complexes, particularly ruthenium(II) complexes.

Two mixed-ligand ruthenium(ii) complexes [Ru(phen)2(cptcp)]2+ (Ru1; phen = 1,10-phenanthroline, cptcp = 2-(4-carbazol-9-yl-phenyl)-1H-1,3,7,8-tetraaza-cyclopenta-[l]-phenanthrene) and [Ru(phen)2(btcpc)]2+ (Ru2; btcpc = 9-butyl-6-(1H-1,3,7,8-tetraaza-cyclo-cyclopenta-[l]-phenanthren-2-yl)-9H-carbazole-3-carbaldehyde) have been synthesised and characterised. The DNA-binding behaviours of the two complexes have been investigated by using spectroscopic and viscosity measurements. Results suggest that the two complexes bind to DNA by intercalation. The photocleavage of plasmid pBR322 DNA indicates that Ru1 exhibits more effective DNA cleavage activity in comparison to that exhibited by Ru2 under the same conditions, and different cleavage mechanisms are determined. Topoisomerase inhibition and DNA strand passage assay confirm that Ru1 may act as an efficient dual inhibitor of topoisomerases I and II, whereas Ru2 may only act as a single inhibitor of topoisomerases II.