The COVID-19 disease is caused by a new strain of the coronavirus family (SARS-CoV-2), and it has affected at present millions of people all over the world. The indispensable role of the main protease (M pro ) in viral replication and gene expression makes this enzyme an attractive drug target. Therefore, inhibition of SARS-CoV-2 M pro as a proposition to halt virus ingression is being pursued by scientists globally. Here we carried out a study with two objectives: the first being to perform comparative protein sequence and 3D structural analysis to understand the effect of 12 point mutations on the active site. Among these, two mutations, viz., Ser46 and Phe134, were found to cause a significant change at the active sites of SARS-CoV-2. The Ser46 mutation present at the entrance of the S5 subpocket of SARS-CoV-2 increases the contribution of other two hydrophilic residues, while the Phe134 mutation, present in the catalytic cysteine loop, can cause an increase in catalytic efficiency of M pro by facilitating fast proton transfer from the Cys145 to His41 residue. It was observed that active site remained conserved among M pro of both SARS-CoVs, except at the entrance of the S5 subpocket, suggesting sustenance of substrate specificity. The second objective was to screen the inhibitory effects of three different data sets (natural products, coronaviruses main protease inhibitors, and FDA-approved drugs) using a structure-based virtual screening approach. A total of 73 hits had a combo score >2.0. Eight different structural scaffold classes were identified, such as one/two tetrahydropyran ring(s), dipeptide/tripeptide/oligopeptide, large (approximately 20 atoms) cyclic peptide, and miscellaneous. The screened hits showed key interactions with subpockets of the active site. Further, molecular dynamics studies of selected screened compounds confirmed their perfect fitting into the subpockets of the active site. This study suggests promising structures that can fit into the SARS-CoV-2 M pro active site and also offers direction for further lead optimization and rational drug design.

A review of various properties of ceramic-reinforced aluminium matrix composites is presented in this paper. The properties discussed include microstructural, optical, physical and mechanical behaviour of ceramic-reinforced aluminium matrix composites and effects of reinforcement fraction, particle size, heat treatment and extrusion process on these properties. The results obtained by many researchers indicated the uniform distribution of reinforced particles with localized agglomeration at some places, when the metal matrix composite was processed through stir casting method. The density, hardness, compressive strength and toughness increased with increasing reinforcement fraction; however, these properties may reduce in the presence of porosity in the composite material. The particle size of reinforcements affected the hardness adversely. Tensile strength and flexural strength were observed to be increased up to a certain reinforcement fraction in the composites, beyond which these were reduced. The mechanical properties of the composite materials were improved by either thermal treatment or extrusion process. Initiation and growth of fine microcracks leading to macroscopic failure, ductile failure of the aluminium matrix, combination of particle fracture and particle pull-out, overload failure under tension and brittle fracture were the failure mode and mechanisms, as observed by previous researchers, during fractography analysis of tensile specimens of ceramic-reinforced aluminium matrix composites.

Ceramic-reinforced aluminium matrix composites have attracted considerable attention in engineering applications as a result of their relatively low costs and characteristic isotropic properties. Reinforcement materials include carbides, nitrides and oxides. In an effort to achieve optimality in structure and properties of ceramic-reinforced metal matrix composites (MMCs), various fabrication and heat treatment techniques have evolved over the last 20 years. In this paper, the status of the research and development in fabrication and heat treatment techniques of ceramic-reinforced aluminium matrix composites is reviewed, with a major focus on material systems in terms of chemical compositions, weight or volume fraction, particle size of reinforcement, fabrication methods and heat treatment procedures. Various optical measurement techniques used by the researchers are highlighted. Also, limitations and needs of the technique in composite fabrication are presented in the literature. The full potential of various methods for fabricating ceramic-reinforced aluminium matrix composites is yet to be explored.

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