Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/135660
Title: STRUCTURAL AND BIOPHYSICAL CHARACTERIZATION OF THE INTERACTION BETWEEN INFLUENZA A NON-STRUCTURAL PROTEIN 1 AND MONOCLONAL ANTIBODIES
Authors: WU JIANPING
Keywords: influenza, non-structural protein 1, monoclonal antibodies, crystallography
Issue Date: 18-Jan-2017
Citation: WU JIANPING (2017-01-18). STRUCTURAL AND BIOPHYSICAL CHARACTERIZATION OF THE INTERACTION BETWEEN INFLUENZA A NON-STRUCTURAL PROTEIN 1 AND MONOCLONAL ANTIBODIES. ScholarBank@NUS Repository.
Abstract: Influenza A virus (IAV) continues to pose great threat to human life, while there is an unmet medical need of available antiviral strategies. To discover alternative strategy, we found two antibodies -- 2H6 and 19H9 specifically targeting IAV Non-structural 1 protein (NS1) which is involved in viral replication and pathogenicity. By X-ray crystallography and HADDOCK simulation, the complementary determining region 2 of heavy chain variable region of 2H6-fragment antigen binding (Fab) was responsible for the binding to NS1 RNA-binding domain (RBD) positions 48 and 49. Intracellular delivery of 2H6-Fab was able to inhibit viral replication by disrupting NS1(RBD)-dsRNA interaction. Furthermore, monoclonal antibody (mAb)-19H9 was determined to bind to the positions 85 and 89 at NS1 effector domain. Y89 is required for activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway. MAb-19H9 was able to reduce viral replication and NS1-PI3K interaction. Thus, both antibodies are good candidates for further development as antiviral agents.
URI: http://scholarbank.nus.edu.sg/handle/10635/135660
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
WuJP.pdf5.58 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

21
checked on May 22, 2019

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.