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Cathepsin L (CTSL), a cysteine protease that can cleave and activate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, could be a promising therapeutic target for coronavirus disease 2019 (COVID-19). However, there is still no clinically available CTSL inhibitor that can be used. Here, we applied Chemprop, a newly trained directed-message passing deep neural network approach, to identify small molecules and FDA-approved drugs that can block CTSL activity to expand the discovery of CTSL inhibitors for drug development and repurposing for COVID-19. We found 5 molecules (Mg-132, Z-FA-FMK, leupeptin hemisulfate, Mg-101 and calpeptin) that were able to significantly inhibit the activity of CTSL in the nanomolar range and inhibit the infection of both pseudotype and live SARS-CoV-2. Notably, we discovered that daptomycin, an FDA-approved antibiotic, has a prominent CTSL inhibitory effect and can inhibit SARS-CoV-2 pseudovirus infection. Further, molecular docking calculation showed stable and robust binding of these compounds with CTSL. In conclusion, this study suggested for the first time that Chemprop is ideally suited to predict additional inhibitors of enzymes and revealed the noteworthy strategy for screening novel molecules and drugs for the treatment of COVID-19 and other diseases with unmet needs.

Iron–nitrogen doped carbon (Fe/N/C) electrocatalysts are among the most promising materials to replace Pt for the oxygen reduction reaction (ORR). Up to now, most work has been devoted to improving the performance of Fe/N/C catalysts by material design, while ignoring the design of the electrode/electrolyte interface environment. Considering the superior ORR performance of Fe/N/C catalysts in alkaline electrolyte, we attempt to construct a proton-deficient environment at the electrode surface to raise the local pH value. An anion-exchange ionomer with H+ blocking ability was chosen as the binder of the iron phthalocyanine (FePc) catalyst, a model molecule for Fe/N/C. The anion-exchange ionomer can increase the interface pH value as compared with commonly used Nafion binder, which was verified by the electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique with CO32–/HCO3– as a probe. This strategy significantly improves the ORR activity and stability of the FePc catalyst in acidic medium.

Carbon atomic layers with encapsulated transition metal nanoparticles exhibit high catalytic activity for the oxygen reduction reaction (ORR), and good tolerance for poisoning species and acid leaching. However, the active sites and catalytic mechanism are not yet clear, mainly due to the highly heterogeneous structure of encapsulated types of catalysts. In this study, we developed a new model catalyst to mimic encapsulated types of catalysts by covering the well-defined active sites of iron phthalocyanine (FePc) with a monolayer of graphene. It was found that the FePc can activate the surface carbon layer to catalyze the ORR. Unlike exposed FePc on graphene, the embedded catalyst is insensitive to poisoning by SCN− ions. The designed model catalyst demonstrates that molecular type active sites, as well as metal nanoparticles, can form encapsulated catalysts for ORR. The simple and well-defined structure of this model catalyst is helpful for investigating the active sites and the catalytic mechanism at the atomic scale. Keywords: Oxygen reduction reaction, Model catalysts, Fe/N/C, Encapsulated catalysts, FePc, Graphene

Poor control of metabolic diseases induces kidney injury, resulting in microalbuminuria, renal insufficiency and, ultimately, chronic kidney disease. The potential pathogenetic mechanisms of renal injury caused by metabolic diseases remain unclear. Tubular cells and podocytes of the kidney show high expression of histone deacetylases known as sirtuins (SIRT1–7). Available evidence has shown that SIRTs participate in pathogenic processes of renal disorders caused by metabolic diseases. The present review addresses the regulatory roles of SIRTs and their implications for the initiation and development of kidney damage due to metabolic diseases. SIRTs are commonly dysregulated in renal disorders induced by metabolic diseases such as hypertensive nephropathy and diabetic nephropathy. This dysregulation is associated with disease progression. Previous literature has also suggested that abnormal expression of SIRTs affects cellular biology, such as oxidative stress, metabolism, inflammation, and apoptosis of renal cells, resulting in the promotion of invasive diseases. This literature reviews the research progress made in understanding the roles of dysregulated SIRTs in the pathogenesis of metabolic disease-related kidney disorders and describes the potential of SIRTs serve as biomarkers for early screening and diagnosis of these diseases and as therapeutic targets for their treatment.