TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds.
TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds.
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DOI：
10.1016/j.antiviral.2009.12.001
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发表时间：
2010-03
影响因子：
7.6
通讯作者：
Ishizaka Y
中科院分区：
文献类型：
--
作者：
Haga S;Nagata N;Okamura T;Yamamoto N;Sata T;Yamamoto N;Sasazuki T;Ishizaka Y
由于严重急性呼吸综合征冠状病毒（SARS-CoV）的爆发可能会再次出现，因此鉴定抗病毒化合物至关重要。以前，我们发现细胞因子TNF-α转化酶（TACE），由SARS-CoV的刺突蛋白（SARS-S蛋白）激活，积极参与病毒进入，这意味着TACE是开发抗病毒化合物的可能靶点。为了证明这种可能性，我们在这里测试了TACE抑制剂对病毒进入的影响。体外和体内数据显示，TACE抑制剂TAPI-2减弱了在慢病毒载体骨架中表达SARS-S蛋白的假型病毒和感染性SARS-CoV的进入。TAPI-2阻断SARS-S蛋白诱导的SARS-CoV受体血管紧张素转换酶2（ACE 2）的脱落和肺组织中TNF-α的产生。由于SARS-S蛋白下调ACE 2被认为是严重临床表现的病因学事件，我们的数据表明TACE拮抗剂阻断SARS-CoV感染并减轻其严重临床结局。
Because outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV) might reemerge, identifying antiviral compounds is of key importance. Previously, we showed that the cellular factor TNF-α converting enzyme (TACE), activated by the spike protein of SARS-CoV (SARS-S protein), was positively involved in viral entry, implying that TACE is a possible target for developing antiviral compounds. To demonstrate this possibility, we here tested the effects of TACE inhibitors on viral entry. In vitro and in vivo data revealed that the TACE inhibitor TAPI-2 attenuated entry of both pseudotyped virus expressing the SARS-S protein in a lentiviral vector backbone and infectious SARS-CoV. TAPI-2 blocked both the SARS-S protein-induced shedding of angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV, and TNF-α production in lung tissues. Since the downregulation of ACE2 by SARS-S protein was proposed as an etiological event in the severe clinical manifestations, our data suggest that TACE antagonists block SARS-CoV infection and also attenuate its severe clinical outcome.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
5.4
作者：
Shih, Yi-Ping;Chen, Chia-Yen;Chen, Yi-Ming Arthur
通讯作者：
Chen, Yi-Ming Arthur
影响因子：
82.9
作者：
Kuba K;Imai Y;Rao S;Gao H;Guo F;Guan B;Huan Y;Yang P;Zhang Y;Deng W;Bao L;Zhang B;Liu G;Wang Z;Chappell M;Liu Y;Zheng D;Leibbrandt A;Wada T;Slutsky AS;Liu D;Qin C;Jiang C;Penninger JM
通讯作者：
Penninger JM
影响因子：
64.8
作者：
MOHLER, KM;SLEATH, PR;BLACK, RA
通讯作者：
BLACK, RA
DOI：
10.1074/jbc.m505111200
发表时间：
2005-08-26
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lambert DW;Yarski M;Warner FJ;Thornhill P;Parkin ET;Smith AI;Hooper NM;Turner AJ
通讯作者：
Turner AJ