Kuiper Benjamin D, Slater Kristin, Spellmon Nicholas, Holcomb Joshua, Medapureddy Prasanna, Muzzarelli Kendall M, Yang Zhe, Ovadia Reuben, Amblard Franck, Kovari Iulia A, Schinazi Raymond F, Kovari Ladislau C
Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Biochem Biophys Res Commun. 2017 Oct 28;492(4):668-673. doi: 10.1016/j.bbrc.2017.03.108. Epub 2017 Mar 22.
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.
寨卡病毒（ZIKV）是一种黄病毒，由埃及伊蚊和白纹伊蚊等白天活动的伊蚊属蚊子传播。以前认为该病毒感染症状较轻，但最近在美洲爆发的寨卡病毒疫情却与更严重的症状以及严重的出生缺陷（如小头畸形）存在因果关系。目前尚无疫苗或抗病毒药物。然而，最近的研究进展表明，病毒NS2B/NS3蛋白酶可能是开发小分子抗病毒药物的合适靶点。为了更好地了解寨卡病毒蛋白酶，我们表达、纯化并鉴定了与波多黎各近期疫情分离株相对应的非连接型和连接型NS2B/NS3蛋白酶。非连接型寨卡病毒蛋白酶比连接型寨卡病毒蛋白酶活性更高，与底物的结合亲和力更强。因此，我们建议在评估或设计寨卡病毒蛋白酶抑制剂时使用非连接型寨卡病毒蛋白酶。此外，相关病毒蛋白酶（如西尼罗河病毒和登革热病毒）的强效抑制剂可能是鉴定和开发寨卡病毒蛋白酶抑制剂的良好起点。
