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- W3037237219 endingPage "114122" @default.
- W3037237219 startingPage "114122" @default.
- W3037237219 abstract "An unprecedented biological function of natural cardenolides independent of their membrane target Na+/K+-ATPase is disclosed. Previously, we reported that cardenolides impart anti-transmissible gastroenteritis coronavirus (anti-TGEV) activity through the targeting of Na+/K+-ATPase and its associated PI3K_PDK1_RSK2 signaling. Swine testis cells with Na+/K+-ATPase α1 knocked down exhibited decreased susceptibility to TGEV infectivity and attenuated PI3K_PDK1_RSK2 signaling. Herein, we further explored a Na+/K+-ATPase-independent signaling axis induced by natural cardenolides that also afforded significant anti-coronaviral activity for porcine TGEV and human HCoV-OC43. Using pharmacological inhibition and gene silencing techniques, we found that this anti-TGEV or anti-HCoV-OC43 activity was caused by JAK1 proteolysis and mediated through upstream activation of Ndfip1/2 and its effector NEDD4. This study provides novel insights into the pharmacological effects of natural cardenolides, and is expected to inform their future development as antiviral agents." @default.
- W3037237219 created "2020-07-02" @default.
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- W3037237219 date "2020-10-01" @default.
- W3037237219 modified "2023-10-16" @default.
- W3037237219 title "Natural cardenolides suppress coronaviral replication by downregulating JAK1 via a Na+/K+-ATPase independent proteolysis" @default.
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- W3037237219 doi "https://doi.org/10.1016/j.bcp.2020.114122" @default.
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