Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/135660
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dc.titleSTRUCTURAL AND BIOPHYSICAL CHARACTERIZATION OF THE INTERACTION BETWEEN INFLUENZA A NON-STRUCTURAL PROTEIN 1 AND MONOCLONAL ANTIBODIES
dc.contributor.authorWU JIANPING
dc.date.accessioned2017-05-17T18:00:16Z
dc.date.available2017-05-17T18:00:16Z
dc.date.issued2017-01-18
dc.identifier.citationWU JIANPING (2017-01-18). STRUCTURAL AND BIOPHYSICAL CHARACTERIZATION OF THE INTERACTION BETWEEN INFLUENZA A NON-STRUCTURAL PROTEIN 1 AND MONOCLONAL ANTIBODIES. ScholarBank@NUS Repository.
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/135660
dc.description.abstractInfluenza 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.
dc.language.isoen
dc.subjectinfluenza, non-structural protein 1, monoclonal antibodies, crystallography
dc.typeThesis
dc.contributor.departmentMICROBIOLOGY & IMMUNOLOGY
dc.contributor.supervisorTAN YEE JOO
dc.contributor.supervisorYUAN YU-REN, ADAM
dc.description.degreePh.D
dc.description.degreeconferredDOCTOR OF PHILOSOPHY
dc.identifier.isiutNOT_IN_WOS
Appears in Collections:Ph.D Theses (Open)

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