Virtual Screening Of Influenza Virus Endonuclease Inhibitors

Influenza is an acute respiratory infection caused by seasonal influenza viruses.It has high morbidity and mortality and is a public health problem of great concern.Now,the most common treatment is vaccine,in addition to some traditional anti-influenza drug treatments.However,when some new influenza spreads,the corresponding vaccine is not immediately available,and many new viruses are highly resistant to traditional anti-influenza drugs,so innovative for targeting contaminated areas of influenza virus is necessary.Research on anti-influenza drugs is imminent.Based on the research and development of the anti-influenza drug Xofluza from Japan's Shionogi Company,this study combined the active molecular data in the ChEMBL database with the protein crystal structure data in the Protein Database to design special virtual screening process with a series of features of this system.Then screenned three commercially available databases of Specs,Chemdiv and Enamine,and 84 potential active compounds were finally screened.Firstly,the activity data and structure of active molecules were downloaded from ChEMBL database,and the molecular structure data in Specs,Chemdiv and Enamine were obtained,Pre-processing operation,such as adding hydrogenation,adding charge were carried out.Analyzing the physicochemical properties of the active molecules obtained from ChEMBL,constructing a physical and chemical screening model,and performing preliminary screening on three preparation databases.Then,using Xofluza as a template,use molecular similarity-based method to screening database.Screening was performed to find molecules with similar spatial structures and electrostatic interactions with Xofluza.After these two steps,the number of molecules in the screening library can be quickly reduced.Subsequently,the protein ligand interaction of the corresponding protein of the endonuclease was analyzed,and the key information was found in the system.The pharmacophore model was constructed to further screen to the preparation database.Then,using the active molecules in ChEMBL and the inactive molecules in MDDR to construct a test set,comparing the enrichment rates of MOE,GOLD and Glide three molecular docking software,and selecting the appropriate docking software for the docking of the system.Screening molecules based on docking scores.Finally,combinning with the interaction between the docking and protein ligands,the final screening of the obtained molecules was performed using an empirical-based method,and calculating combined free energy to determine the effectiveness of the potential active molecules.Based on the relevant information of Xofluza and biological activity data related to endonuclease,this paper constructed a series of virtual screening processes.The research of our study will help to find innovative anti-influenza drugs that can be targeted to the conserved regions of influenza virus,and it has certain guiding significance for the construction of virtual screening processes of various systems.