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.

Colorimetric Determination of Chloridion in Domestic Water Based on the Wavelength Shift of CsPbBr_(3) Perovskite Nanocrystals via Halide Exchange

Cubic phase CsPbBr_(3)perovskite nanocrystals(PNCs)was prepared by a high-temperature hot-injection method.The high photoluminescence quantum yield(PLQY)of as-prepared CsPbBr_(3)PNCs was 87%,which can be used for the determination of chloridion in domestic water samples based on their wavelength-shift characteristics via halide exchange.The proposal approach for the determination of chloridion reveals a linear correlation ranged from 10 to 200μM of the chloridion concentration and the wavelength shift of CsPbBr_(3)PNCs with a correlation coe fficient of R^(2)=0.9956.The as-mentioned method reveals neglectable responses towards those co-existing ions in the water aside from chloridion,due to the quick exchange between Cl and Br and the outstanding color change caused by wavelength shift.The strategy has been applied to the determination of chloridion in water samples with the recoveries of 98.9–104.2%and the limit of detection(LOD)of 4μM.These results show that the suggested approach is promising for the development of novel fluorescence detection for chloridion in water.