title: The many faces of the flavivirus NS1 protein offer a multitude of options for inhibitor design.
abstract: The flavivirus non-structural protein, NS1, is an unusual viral gene product. Despite the recent unveiling of its atomic structure (Akey et al., 2014), and a growing list of host molecules with which it has been found associated, the primary function of NS1 remains elusive. It assumes many diverse roles including direct participation in the flaviviral replication complex and virion maturation. In its secreted form it is a hexameric lipoparticle that is involved in systemic immune and endothelial cell modulation. In this review we highlight recent advances in elucidating the molecular mechanisms underpinning NS1 function and present the current state of play and some future prospects for NS1 targeted antiviral strategies. This article forms part of a symposium on flavivirus drug discovery in Antiviral Research.
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Watterson
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Naphak
authors.initials: N
authors.lastname: Modhiran
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: p.young@uq.edu.au.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Young
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D015195:Drug Design; D005416:Flavivirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D012323:RNA Processing, Post-Transcriptional; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D008055:Lipids; C100315:NS1 protein, Flavivirus; D017361:Viral Nonstructural Proteins
keywords: Antiviral; Complement; Dengue; Flavivirus; Inhibitors