Increased activity of unlinked Zika virus NS2B/NS3 protease compared to linked Zika virus protease.

Autor: Kuiper BD; Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA., Slater K; Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA., Spellmon N; Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA., Holcomb J; Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA., Medapureddy P; Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA., Muzzarelli KM; Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA., Yang Z; Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA., Ovadia R; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA., Amblard F; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA., Kovari IA; Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA., Schinazi RF; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA., Kovari LC; Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA. Electronic address: kovari@med.wayne.edu.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2017 Oct 28; Vol. 492 (4), pp. 668-673. Date of Electronic Publication: 2017 Mar 22.
DOI: 10.1016/j.bbrc.2017.03.108
Abstrakt: Zika virus (ZIKV) is a flavivirus spread by daytime-active Aedes spp. mosquitoes such as A. aegypti and A. albopictus. Previously thought to be a mild infection, the latest ZIKV outbreak in the Americas is causally associated with more severe symptoms as well as severe birth defects, such as microcephaly. Currently no vaccine or antiviral exists. However, recent progress has demonstrated the viral NS2B/NS3 protease may be a suitable target for the development of small-molecule antiviral agents. To better understand the ZIKV protease, we expressed, purified, and characterized unlinked and linked NS2B/NS3 protease corresponding to an isolate from the recent outbreak in Puerto Rico. Unlinked ZIKV protease is more active and binds substrate with greater affinity than linked ZIKV protease. Therefore, we propose that unlinked ZIKV protease be used when evaluating or designing ZIKV protease inhibitors. Additionally, potent inhibitors of related viral proteases, like West Nile Virus and Dengue virus, may serve as advanced starting points to identify and develop ZIKV protease inhibitors.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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