期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 332, 期 -, 页码 129-137出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2017.04.017
关键词
Cardenolide; Coronavirus; Na+/K+ -ATPase; Oleandrin; Porcine transmissible gastroenteritis virus; Reevesioside
资金
- National Health Research Institutes, Taiwan, R.O.C.
- Ministry of Science and Technology, Taiwan, R.O.C. [NSC 102-2628-B-400-002-MY3, MOST 104-2811-B-400-013, MOST 105-2325-B-400-005]
A series of naturally occurring cardenolides that exhibit potent anti-transmissible gastroenteritis virus (TGEV) activity in swine testicular (ST) cells has been identified. In an immunofluorescence assay, these cardenolides were found to diminish the expressions of TGEV nucleocapsid and spike protein, which was used as an indication for viral replication; block TGEV infection induced apoptosis and cytopathic effects; and impart the same trend of inhibitory activity against Na+/K+-ATPase as for anti-TGEV activity. The viral titer inhibition was found to take place in a dose-dependent manner. Knocking down expression of Na+/K+-ATPase, the cellular receptor of cardenolides, in ST cells was found to significantly impair the susceptibility of ST cells to TGEV infectivity. Thus, we have identified Na+/K+-ATPase as an anti-viral drug target and its antagonists, cardenolides, a novel class of anti-TGEV agents. (C) 2017 Elsevier Inc. All rights reserved.
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