Identification of anti-viral activity of the cardenolides, Na+/K+-ATPase inhibitors, against porcine transmissible gastroenteritis virus
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 prote...
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| Veröffentlicht in: | Toxicology and applied pharmacology 2017-10, Vol.332, p.129-137 |
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| container_title | Toxicology and applied pharmacology |
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| creator | Yang, Cheng-Wei Chang, Hsin-Yu Hsu, Hsing-Yu Lee, Yue-Zhi Chang, Hsun-Shuo Chen, Ih-Sheng Lee, Shiow-Ju |
| description | 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.
[Display omitted]
•Cardenolides were identified as a novel class of anti-TGEV agents.•Cardenolides diminished TGEV replication/viral titers in a dose dependent manner.•Cardenolides blocked TGEV infection induced apoptosis and cytopathic effect.•These cardenolides imparted the same trend of inhibitory activity for Na+/K+-ATPase.•Na+/K+-ATPase was identified as an anti-viral drug target. |
| doi_str_mv | 10.1016/j.taap.2017.04.017 |
| format | Article |
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[Display omitted]
•Cardenolides were identified as a novel class of anti-TGEV agents.•Cardenolides diminished TGEV replication/viral titers in a dose dependent manner.•Cardenolides blocked TGEV infection induced apoptosis and cytopathic effect.•These cardenolides imparted the same trend of inhibitory activity for Na+/K+-ATPase.•Na+/K+-ATPase was identified as an anti-viral drug target.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2017.04.017</identifier><identifier>PMID: 28438630</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Animals ; Antibodies, Monoclonal - pharmacology ; Antiviral Agents - pharmacology ; Apoptosis - drug effects ; Cardenolide ; Cardenolides - pharmacology ; Coronavirus ; Dose-Response Relationship, Drug ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Gene Silencing ; INFECTIVITY ; INHIBITION ; Na+/K+-ATPase ; Nucleocapsid Proteins - genetics ; Nucleocapsid Proteins - metabolism ; Oleandrin ; Porcine transmissible gastroenteritis virus ; Reevesioside ; RNA, Viral - isolation & purification ; SODIUM IONS ; Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors ; Sodium-Potassium-Exchanging ATPase - metabolism ; Swine ; Transmissible gastroenteritis virus - drug effects ; Transmissible gastroenteritis virus - physiology ; Virus Replication ; VIRUSES</subject><ispartof>Toxicology and applied pharmacology, 2017-10, Vol.332, p.129-137</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><rights>2017 Elsevier Inc. All rights reserved. 2017 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c434t-1ef7f61a2af6d686699bc4837b8d6a1967c3af82e984461630f3401aeb13f2983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0041008X17301746$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28438630$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22722933$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Cheng-Wei</creatorcontrib><creatorcontrib>Chang, Hsin-Yu</creatorcontrib><creatorcontrib>Hsu, Hsing-Yu</creatorcontrib><creatorcontrib>Lee, Yue-Zhi</creatorcontrib><creatorcontrib>Chang, Hsun-Shuo</creatorcontrib><creatorcontrib>Chen, Ih-Sheng</creatorcontrib><creatorcontrib>Lee, Shiow-Ju</creatorcontrib><title>Identification of anti-viral activity of the cardenolides, Na+/K+-ATPase inhibitors, against porcine transmissible gastroenteritis virus</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>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.
[Display omitted]
•Cardenolides were identified as a novel class of anti-TGEV agents.•Cardenolides diminished TGEV replication/viral titers in a dose dependent manner.•Cardenolides blocked TGEV infection induced apoptosis and cytopathic effect.•These cardenolides imparted the same trend of inhibitory activity for Na+/K+-ATPase.•Na+/K+-ATPase was identified as an anti-viral drug target.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antiviral Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Cardenolide</subject><subject>Cardenolides - pharmacology</subject><subject>Coronavirus</subject><subject>Dose-Response Relationship, Drug</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Gene Silencing</subject><subject>INFECTIVITY</subject><subject>INHIBITION</subject><subject>Na+/K+-ATPase</subject><subject>Nucleocapsid Proteins - genetics</subject><subject>Nucleocapsid Proteins - metabolism</subject><subject>Oleandrin</subject><subject>Porcine transmissible gastroenteritis virus</subject><subject>Reevesioside</subject><subject>RNA, Viral - isolation & purification</subject><subject>SODIUM IONS</subject><subject>Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors</subject><subject>Sodium-Potassium-Exchanging ATPase - metabolism</subject><subject>Swine</subject><subject>Transmissible gastroenteritis virus - drug effects</subject><subject>Transmissible gastroenteritis virus - physiology</subject><subject>Virus Replication</subject><subject>VIRUSES</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UV1rFDEUDWKxa_UP-CABH-tM80VmBkQoRW1pUR8q-BbuZJLdu-wmS5Iu9B_0Z5thtbQvPh2Se-45995DyDvOWs64Plu3BWDXCsa7lqm2wguy4GzQDZNSviQLxhRvGOt_H5PXOa8ZY4NS_BU5Fr2SvZZsQR6uJhcKerRQMAYaPYX6bvaYYEPBFtxjuZ-_y8pRC6nS4wYnlz_S73B6dn3anN_-hOwohhWOWGKqFVgChlzoLiaLwdGSIOQt5ozjxtEl5JJitXUJC2Zave7yG3LkYZPd2794Qn59_XJ7cdnc_Ph2dXF-01glVWm4853XHAR4Pele62EYreplN_aTBj7ozkrwvXBDr5TmdUcvFePgRi69GHp5Qj4fdHd349ZNto5RNzW7hFtI9yYCmueVgCuzjHvTcSa5kFXgw0Eg5oImWyzOrmwMwdlihOiEGOTMEgeWTTHn5PyjA2dmTs-szZyemdMzTJkKten909keW_7FVQmfDgRXL7RHl2Z_F6ybMM32U8T_6f8BCEWuvg</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>Yang, Cheng-Wei</creator><creator>Chang, Hsin-Yu</creator><creator>Hsu, Hsing-Yu</creator><creator>Lee, Yue-Zhi</creator><creator>Chang, Hsun-Shuo</creator><creator>Chen, Ih-Sheng</creator><creator>Lee, Shiow-Ju</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>20171001</creationdate><title>Identification of anti-viral activity of the cardenolides, Na+/K+-ATPase inhibitors, against porcine transmissible gastroenteritis virus</title><author>Yang, Cheng-Wei ; Chang, Hsin-Yu ; Hsu, Hsing-Yu ; Lee, Yue-Zhi ; Chang, Hsun-Shuo ; Chen, Ih-Sheng ; Lee, Shiow-Ju</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-1ef7f61a2af6d686699bc4837b8d6a1967c3af82e984461630f3401aeb13f2983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antiviral Agents - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Cardenolide</topic><topic>Cardenolides - pharmacology</topic><topic>Coronavirus</topic><topic>Dose-Response Relationship, Drug</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Gene Silencing</topic><topic>INFECTIVITY</topic><topic>INHIBITION</topic><topic>Na+/K+-ATPase</topic><topic>Nucleocapsid Proteins - genetics</topic><topic>Nucleocapsid Proteins - metabolism</topic><topic>Oleandrin</topic><topic>Porcine transmissible gastroenteritis virus</topic><topic>Reevesioside</topic><topic>RNA, Viral - isolation & purification</topic><topic>SODIUM IONS</topic><topic>Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors</topic><topic>Sodium-Potassium-Exchanging ATPase - metabolism</topic><topic>Swine</topic><topic>Transmissible gastroenteritis virus - drug effects</topic><topic>Transmissible gastroenteritis virus - physiology</topic><topic>Virus Replication</topic><topic>VIRUSES</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Cheng-Wei</creatorcontrib><creatorcontrib>Chang, Hsin-Yu</creatorcontrib><creatorcontrib>Hsu, Hsing-Yu</creatorcontrib><creatorcontrib>Lee, Yue-Zhi</creatorcontrib><creatorcontrib>Chang, Hsun-Shuo</creatorcontrib><creatorcontrib>Chen, Ih-Sheng</creatorcontrib><creatorcontrib>Lee, Shiow-Ju</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Cheng-Wei</au><au>Chang, Hsin-Yu</au><au>Hsu, Hsing-Yu</au><au>Lee, Yue-Zhi</au><au>Chang, Hsun-Shuo</au><au>Chen, Ih-Sheng</au><au>Lee, Shiow-Ju</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of anti-viral activity of the cardenolides, Na+/K+-ATPase inhibitors, against porcine transmissible gastroenteritis virus</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2017-10-01</date><risdate>2017</risdate><volume>332</volume><spage>129</spage><epage>137</epage><pages>129-137</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><abstract>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.
[Display omitted]
•Cardenolides were identified as a novel class of anti-TGEV agents.•Cardenolides diminished TGEV replication/viral titers in a dose dependent manner.•Cardenolides blocked TGEV infection induced apoptosis and cytopathic effect.•These cardenolides imparted the same trend of inhibitory activity for Na+/K+-ATPase.•Na+/K+-ATPase was identified as an anti-viral drug target.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28438630</pmid><doi>10.1016/j.taap.2017.04.017</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES Animals Antibodies, Monoclonal - pharmacology Antiviral Agents - pharmacology Apoptosis - drug effects Cardenolide Cardenolides - pharmacology Coronavirus Dose-Response Relationship, Drug Epithelial Cells - drug effects Epithelial Cells - metabolism Gene Silencing INFECTIVITY INHIBITION Na+/K+-ATPase Nucleocapsid Proteins - genetics Nucleocapsid Proteins - metabolism Oleandrin Porcine transmissible gastroenteritis virus Reevesioside RNA, Viral - isolation & purification SODIUM IONS Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors Sodium-Potassium-Exchanging ATPase - metabolism Swine Transmissible gastroenteritis virus - drug effects Transmissible gastroenteritis virus - physiology Virus Replication VIRUSES |
| title | Identification of anti-viral activity of the cardenolides, Na+/K+-ATPase inhibitors, against porcine transmissible gastroenteritis virus |
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