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Title: Serpin-based SKI-1/S1P inhibitors against Old and New World arenaviruses
Authors: Chan, Mable W. S.
Supervisor: Ball, T. Blake (Medical Microbiology)
Examining Committee: Stetefeld, Jorg (Chemistry) Fowke, Keith (Medical Microbiology)
Graduation Date: May 2011
Keywords: arenaviruses
Issue Date: 12-Apr-2011
Abstract: The importance of arenavirus glycoprotein processing has only been understood within the past decade, with the majority of work focused on the Old World arenaviruses. Evidence has shown that SKI-1/S1P (subtilisin kexin isozyme-1/site 1 protease) is the cellular protease responsible for glycoprotein cleavage in Old and New World arenaviruses. Furthermore, glycoprotein cleavage is shown to be necessary for the production of infectious virus particles in Lassa and Junín viruses. In this thesis, evidence is provided that the recently emerged Chapare virus (New World) is also processed by SKI-1/S1P. Additionally, novel serpin-based SKI-1 inhibitors were shown to effectively prevent SKI-1 mediated cleavage. Using a wide panel of recombinant vesicular stomatitis viruses expressing New World arenavirus glycoproteins, these inhibitors were capable of significantly reducing viral titres. This provides strong evidence that SKI-1 inhibitors can be used as an effective treatment against the majority of New World Clade B arenaviruses and LASV in vivo.
Appears in Collection(s):FGS - Electronic Theses & Dissertations (Public)

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