國家衛生研究院 NHRI:Item 3990099045/12723
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    题名: Natural cardenolides suppress coronaviral replication by downregulating JAK1 via a Na(+)/K(+)-ATPase independent proteolysis
    作者: Yang, CW;Hsu, HY;Chang, HY;Lee, YZ;Lee, SJ
    贡献者: Institute of Biotechnology and Pharmaceutical Research
    摘要: 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.
    日期: 2020-10
    關聯: Biochemical Pharmacology. 2020 Oct;180:Article number 114122.
    Link to: http://dx.doi.org/10.1016/j.bcp.2020.114122
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0006-2952&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000579310000037
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85087486474
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