Active constituents and mechanisms of Respiratory Detox Shot, a traditional Chinese medicine prescription, for COVID-19 control and prevention: Network-molecular docking-LC–MS^E analysis

Objective: Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot(RDS), was developed based on a classical prescription of traditional Chinese medicine(TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019(COVID-19), have been shown. However,the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS.Methods: To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein–protein interaction(PPI) network, and cluster analysis;further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS.Results: For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent–target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target–constitu ent–disease network. Twelve disease pathways attributed to the Lung–Large Intestine meridians, with six and five attributed to the Kidney–Urinary Bladder and Stomach–Spleen meridians, respectively. Onehundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-23-chymotrypsin-like protease(3 CLpro), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3 CLproinhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode,the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches.Conclusion: RDS acts primarily in the Lung–Large Intestine, Kidney–Urinary Bladder and Stomach–Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS’s dual effects of healthstrengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.

Recent advances in carbonized non-noble metal–organic frameworks for electrochemical catalyst of oxygen reduction reaction

The non-noble metal oxygen reduction reaction(ORR) catalysts prepared by carbonization of metal–organic framework(MOF) have attracted more and more attentions in the fields of fuel cells and metal-air batteries due to their unique intrinsic advantages such as high catalytic activity, low price, simple synthesis and good adaptability. Different from the study of traditional high active noble metal catalysts, this review systematically summarizes recent developments on non-noble metal(Fe,Co, Cu, Ni, Mn and Mo) ORR catalysts prepared by various MOFs carbonization in different metal centers. The effects of synthesis strategies and pyrolysis conditions on the catalyst properties are discussed. Meanwhile, the key parameters of catalytic performances(including active sites, dispersed state and specific surface area) are discussed and the prospect is presented. It is expected that this review will provide effective guidance for future studies on carbonized non-noble MOFs for ORR electrochemical catalyst.