The active ingredients of Huanglian Jiedu Decoction in treating COVID- 19 based on network pharmacology, molecular docking and molecular dynamics simulation

Objective:To explore the active ingredients of Huanglian Jiedu Decoction(HLJD)for the treatment of COVID-19 and to further verify the combination mode.Methods:The TCMSP database was used to search for HLJD active ingredients and targets.COVID-19 targets were collected from GeneCards,DisGeNET and OMIM databases.Material-active-ingredients-targets(gene)network and targets protein-protein interaction network were constructed using Cytoscape 3.8.0 and the STRING database.GO functional enrichment analysis and KEGG pathway enrichment analysis of core targets were performed using R software.Cytoscape 3.8.0 was used to build“compound-targets-pathways”to predict HLJD mechanisms,and active ingredients were used as ligands to molecularly dock with SARS-CoV-23CL hydrolase,Spike glycoprotein and ACE2.The binding energy was calculated by molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area method,and intermolecular interactions and the contribution of each residue to the binding free energy were analyzed.Results:Four medicinal materials,66 compounds and 219 targets were identified.It is found that the Protein-Protein Interaction core network contained 35 HLJD key targets proteins for COVID-19 treatment.705 GO functional enrichment entries(P<0.05)were produced;while KEGG pathway enrichment analysis identified 142 pathways(P<0.05)involving the Tumor Necrosis Factor signaling pathway and Interleukin-17 signaling pathway,etc.The binding energies of Kihadanin A,Palmidin A,Obacunone and Hispidone are much smaller than those of the currently reported clinical drugs with anti-SARS-CoV-2 drugs.The results of the binding energy indicate that van der Waals force is the main driving force for enzyme-substrate combination,whereas the electrostatic interaction and non-polar solvents contribute less.Conclusion:The“multi-component-multi-targets-multi-pathway”synergy of HLJD,which binds to SARSCoV-23CL hydrolase,Spike glycoprotein and ACE2,can act on targets Heat Shock Protein 90 Alpha Family Class A Member 1,Adrenoceptor Beta 2,Checkpoint Kinase 1,Peroxisome Proliferator-Activated Receptor Gamma and Mitogen-activated protein kinase 14 to regulate multiple signal pathways,and it may have a therapeutic effect on COVID-19.

Colloidal CsPbBr3 perovskite nanocrystal films as electrochemiluminescence emitters in aqueous solutions

Perovskite nanocrystals （NCs）, which have emerged as a new class of phosphors with superb luminescence properties and bandgaps that can be easily tuned using chemical methods, have generated tremendous interest for a wide variety of applications where colloidal quantum dots have been very successful as carrier sources. In this study, self-assembled films of CsPbBr3 NCs were produced via drop casting of colloidal NCs onto glassy carbon electrodes （GCEs） to form an NC film-modified electrode. The possible fabrication process of the CsPbBr3 NCs films was discussed. We further studied the anodic electrochemiluminescence （ECL） behavior of the perovskite CsPbBr3 NCs film using cyclic voltammetry with tripropylamine （TPA） as a coreactant, and a possible ECL mechanism was proposed. Briefly, TPA was oxidized to produce strongly reducing radical spedes, which can react with electrochemically oxidized CsPbBr3 NCs to generate excited CsPbBr3 NCs＊ capable of light emission. The relative stability of the ECL emission of the CsPbBr3 NC films under aqueous conditions was also investigated, and it was found that they showed operational stability over the first three hours, indicating suitable reliability for application as sensing materials. The results suggested that semiconducting perovskite NCs have great potential for application in the ECL field.