Table_3_Discovery of Multitarget-Directed Ligands Against Influenza A Virus From Compound Yizhihao Through a Predictive System for Compound-Protein In.xlsx (73.91 kB)
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Table_3_Discovery of Multitarget-Directed Ligands Against Influenza A Virus From Compound Yizhihao Through a Predictive System for Compound-Protein Interactions.xlsx

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posted on 11.02.2020, 05:00 authored by Lvjie Xu, Wen Jiang, Hao Jia, Lishu Zheng, Jianguo Xing, Ailin Liu, Guanhua Du

Influenza A virus (IAV) is a threat to public health due to its high mutation rate and resistance to existing drugs. In this investigation, 15 targets selected from an influenza virus–host interaction network were successfully constructed as a multitarget virtual screening system for new drug discovery against IAV using Naïve Bayesian, recursive partitioning, and CDOCKER methods. The predictive accuracies of the models were evaluated using training sets and test sets. The system was then used to predict active constituents of Compound Yizhihao (CYZH), a Chinese medicinal compound used to treat influenza. Twenty-eight compounds with multitarget activities were selected for subsequent in vitro evaluation. Of the four compounds predicted to be active on neuraminidase (NA), chlorogenic acid, and orientin showed inhibitory activity in vitro. Linarin, sinensetin, cedar acid, isoliquiritigenin, sinigrin, luteolin, chlorogenic acid, orientin, epigoitrin, and rupestonic acid exhibited significant effects on TNF-α expression, which is almost consistent with predicted results. Results from a cytopathic effect (CPE) reduction assay revealed acacetin, indirubin, tryptanthrin, quercetin, luteolin, emodin, and apigenin had protective effects against wild-type strains of IAV. Quercetin, luteolin, and apigenin had good efficacy against resistant IAV strains in CPE reduction assays. Finally, with the aid of Gene Ontology biological process analysis, the potential mechanisms of CYZH action were revealed. In conclusion, a compound-protein interaction-prediction system was an efficient tool for the discovery of novel compounds against influenza, and the findings from CYZH provide important information for its usage and development.

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