The SARS coronavirus 3C-like proteinase is recognized as a potential drug design target for the treatment of severe acute respiratory syndrome. In the past few years, much work has been done to understand the catalytic mechanism of this target protein and to design its selective inhibitors. The protein exists as a dimer/monomer mixture in solution and the dimer was confirmed to be the active species for the enzyme reaction. Quantitative dissociation constants have been reported for the dimer by using analytic ultracentrifuge, gel filtration and enzyme assays. Though the enzyme is a cysteine protease with a chymotrypsin fold, SARS 3C-like proteinase follows the general base catalytic mechanism similar to chymotrypsin. As the enzyme can cut eleven different sites on the viral polyprotein, the substrate specificity has been studied by synthesized peptides corresponding or similar to the cleavage sites on the polyprotein. Predictive model was built for substrate structure and activity relationships and can be applied in inhibitor design. Due to the lack of potential drugs for the treatment of SARS, the discovery of inhibitors against SARS 3C-like proteinase, which can potentially be optimized as drugs appears to be highly desirable. Various groups have been working on inhibitor discovery by virtual screening, compound library screening, modification of existing compounds or natural products. High-throughput in vitro assays, auto-cleavage assays and viral replication assays have been developed for inhibition activity tests. Inhibitors with IC50 values as low as 60 nM have been reported.
Benzimidazole derivatives are remarkably effective compounds to many diseases and may have the potential to be the first effective therapy against Ebola virus. Therefore, it is of great importance to develop specific design software and sustainable industrial synthetic routes for the development of effective and clinically relevant benzimidazole compounds.
Simple and reliable mass production of platinum-based alloy catalysts with excellent activity and stability is an enormous challenge for the wide commercialization of proton-exchange membrane fuel cells (PEMFC), especially those with ultralow loading of Pt. Herein, an economical, highly durable, and efficient catalyst consisting of structurally ordered intermetallic Pt 3 Co alloy nanoparticles with ultralow Pt loading (1.4 wt %) supported on hierarchically porous carbon structure (three-dimensional, 3D Pt 3 Co/C) were synthesized with large-scale production by the NaCl-template-assisted approach. The obtained best sample, 3D Pt 3 Co/C#1, exhibited mass activities of 11.56 and 0.70 A mg Pt −1 for oxygen reduction reactions (ORRs) in alkaline and acidic electrolytes, which are 60.8 and 6.4 times those of commercial Pt/C, respectively. Furthermore, the 3D Pt 3 Co/C#1 exhibited excellent stability both in acidic and alkaline electrolytes, with almost no decay of the half-wave potential after 5000 potential cycles. This work proposes a new high-yielding, simple, and environmentally friendly method to fabricate excellent Ptbased alloy electrocatalysts with ultralow loading of Pt, which opens up new hopes for the development of PEMFC.
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