Preliminary exploration of the mechanism of Qingfei Paidu decoction against novel coronavirus pneumonia based on network pharmacology and molecular docking technology / 药学学报

Traditional Chinese medicine (TCM) network pharmacology and molecular docking technology were applied to explore the mechanism of anti-coronavirus pneumonia (coronavirus disease 2019, COVID-19) of Qingfei Paidu decoction. The Chinese Pharmacopoeia (2015 edition) and Traditional Chinese Medicine Systems Pharmacology (TCMSP), OMIM (Online Mendelian Inheritance in Man), GeneCard, STRING, and others online databases are used for building a series of network, and selecting the core target and analyzing the signal pathway. Finally, we make molecular docking predictions for the important compounds. The results showed that the Qingfei Paidu decoction compound-pneumonia target network contained 292 compounds and 214 corresponding targets, and the core targets involved AKT1 (AKT serine/threonine kinase 1), IL6 (interleukin 6), MAPK8 (mitogen-activated protein kinase 8), MAPK1 (mitogen-activated protein kinase 1), and JUN (jun proto-oncogene). GO (Gene Ontology) function enrichment analysis yielded 858 GO entries, and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment screening yielded 122 related pathways, including hypoxia inducible factor-1 (HIF-1) and Toll-like receptor (TLRs) signaling pathways related to pneumonia, as well as T-cell receptor (TCR) signaling pathway related to lung injury protection. The molecular docking results showed that some core compounds of the Chinese herbal medicine of Qingfei Paidu decoction have a certain degree of affinity for 2019-novel coronavirus (2019-nCoV) main protease (3C-like protease, 3CLpro) and angiotensin-converting enzyme 2 (ACE2). In this paper, we preliminarily explored the potential therapeutic mechanism for Qingfei Paidu decoction to against COVID-19 and predicted the active ingredients. We hope that the results will help to the further study on the active ingredients and mechanism of Qingfei Paidu decoction to COVID-19.

Synthesis, activity determination of tropane compounds as muscarinic M3 receptor antagonists and quantitative relationship between their molecular structure and activity / 上海交通大学学报（医学版）

Objective • To provide theoretical guidance for the design of molecules with high activity by building the quantitative structure-activity relationship (QSAR) model for tropane compounds as muscarinic M3 receptor antagonists. Methods • Six compounds (J1-J6) were prepared with 3α-hydroxy-tropane (J0) as the starting material by modifying the structure in C-3α position of the tropane skeleton. The antagonistic activity of new tropane compounds to muscarinic M3 receptors on tracheal rings of guinea pigs was evaluated by functional assays in vitro. The antagonistic parameters (pA2) of new tropane compounds prepared in this paper and former studies were applied to construct the QSAR model. The information about structural optimization was acquired by analyzing the effect of steric field and electrostatic field of model on activity of tropane compounds. Results • The six new tropane compounds showed obvious antagonistic activity against M3 receptors. Among them, J4 had the greatest activity (pA2=7.992). The cross-validation correlation coefficient squared (q2) and the non-cross-validated correlation coefficient squared (r2) of the QSAR model were 0.585 and 0.993, respectively. Conclusion • The antagonistic activity to muscarinic M3 receptors can be obviously improved, when the conjugating extent of π-bonds is large and O or N atoms participate in conjugation on the rings in the R-substituting group at C-3α position of the compounds.

Synthesis, activity determination of tropane compounds as muscarinic M3 receptor antagonists and quantitative relationship between their molecular structure and activity / 上海交通大学学报（医学版）

Objective · To provide theoretical guidance for the design of molecules with high activity by building the quantitative structure-activity relationship (QSAR) model for tropane compounds as muscarinic M3 receptor antagonists. Methods · Six compounds (J1-J6) were prepared with3α-hydroxy-tropane (J0) as the starting material by modifying the structure in C-3α position of the tropane skeleton. The antagonistic activity of new tropane compounds to muscarinic M3 receptors on tracheal rings of guinea pigs was evaluated by functional assays in vitro. The antagonistic parameters (pA2) of new tropane compounds prepared in this paper and former studies were applied to construct the QSAR model. The information about structural optimization was acquired by analyzing the effect of steric field and electrostatic field of model on activity of tropane compounds. Results · The six new tropane compounds showed obvious antagonistic activity against M3 receptors. Among them, J4 had the greatest activity (pA2=7.992). The cross-validation correlation coefficient squared (q2) and the non-cross-validated correlation coefficient squared (r2) of the QSAR model were 0.585 and 0.993, respectively.Conclusion · The antagonistic activity to muscarinic M3 receptors can be obviously improved, when the conjugating extent of π-bonds is large and O or N atoms participate in conjugation on the rings in the R-substituting group at C-3α position of the compounds.

BIOLOGICAL ASPECTS IN THE MEMBRANE BIOREACTOR / 微生物学通报

For the efficient interception performance of the membrane, some biological aspect in membrane bioreactor are different from those in the activated sludge process. The physiological and biochemical characteristics of microbial community, activated sludge, and microbial products in the membrane bioreactor are illustrated in this paper.