Theoretical Simulation Study On Neuraminidase Of Influenza A(H7N9) Virus And Its Potential Small Molecule Inhibitors

Influenza virus is the causative agent of influenza,and influenza virus infection usually causes a variety of diseases,such as fever,cough,sore throat,muscle pain,and life-threatening pneumonia.Influenza virus is mainly divided into three types: A,B,and C.The antigenic variation of A type is the highest,which has caused many worldwide pandemic.The H7N9 flu virus was discovered for the first time in the end of March 2013 in Shanghai and Anhui.From then on,numbers of H7N9 cases were diagnosed and the confirmed and dead people are increasing.H7N9 influenza virus,a new type virus,is the first discovery in the world,and the degree of variation of influenza virus sequence has attracted worldwide attention.The prevention and control of influenza virus mainly rely on vaccines and antiviral drugs.In recent years,the worldwide use of influenza vaccine has confirmed its key role in prevention,especially for the seasonal flu vaccine defense.However,because of vaccine effectiveness mainly depends on the preparation of vaccine virus strains and antigen variation exists in different influenza A virus subtype,the vaccine is difficult to completely control the disease.Therefore,drug treatment is still an important way to prevention and control of influenza.Neuraminidase(NA)plays a key role in the life cycle of influenza virus.NA can catalyze the dissociation of N-acetyl neuraminic acid and adjacent oligosaccharide D-galactose or D-galactosamine alpha(2,6)or alpha(2,3)ketone glycoside bond in terminal sialic acid.And in the process,NA could assist the release of progeny virus from the surface of the infected host cells,and further make progeny virus infect new target cells.Because of its role in influenza virus,NA become the new target of anti influenza virus drug.In this study,H7N9 NA was selected as the object.Virtual screening,molecular dynamics simulation,and steered molecular dynamics simulation method were applied to investigate the potential inhibitory mechanism and binding process of a new natural small molecule to H7N9 NA.The main contents are divided into two aspects as follows:1、Investigating and verifying the combination of natural small molecule which screened from the ZINC database,and providing theoretical clues for NA inhibitors design.2、Exploring the detachment/binding process and dynamic behavior of small molecules by using steered molecular dynamics method.Further studying the influence of small molecule to the catalytic site of NA,and seeking the inhibition mechanism.