{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:10:52Z","timestamp":1782274252774,"version":"3.54.5"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T00:00:00Z","timestamp":1601164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/L015293\/1"],"award-info":[{"award-number":["BB\/L015293\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFD0501404"],"award-info":[{"award-number":["2018YFD0501404"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFD0501103"],"award-info":[{"award-number":["2017YFD0501103"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009449","name":"Petplan Charitable Trust","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100009449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Influenza A virus is a major global pathogen of humans, and there is an unmet need for effective antivirals. Current antivirals against influenza A virus directly target the virus and are vulnerable to mutational resistance. Harnessing an effective host antiviral response is an attractive alternative. We show that brief exposure to low, non-toxic doses of thapsigargin (TG), an inhibitor of the sarcoplasmic\/endoplasmic reticulum (ER) Ca2+ ATPase pump, promptly elicits an extended antiviral state that dramatically blocks influenza A virus production. Crucially, oral administration of TG protected mice against lethal virus infection and reduced virus titres in the lungs of treated mice. TG-induced ER stress unfolded protein response appears as a key driver responsible for activating a spectrum of host antiviral defences that include an enhanced type I\/III interferon response. Our findings suggest that TG is potentially a viable host-centric antiviral for the treatment of influenza A virus infection without the inherent problem of drug resistance.<\/jats:p>","DOI":"10.3390\/v12101093","type":"journal-article","created":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T22:24:42Z","timestamp":1601245482000},"page":"1093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Thapsigargin at Non-Cytotoxic Levels Induces a Potent Host Antiviral Response that Blocks Influenza A Virus Replication"],"prefix":"10.3390","volume":"12","author":[{"given":"Leah V.","family":"Goulding","sequence":"first","affiliation":[{"name":"School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Sutton Bonington LE12 5RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9348-4336","authenticated-orcid":false,"given":"Jiayun","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Sutton Bonington LE12 5RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9797-6493","authenticated-orcid":false,"given":"Zhimin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8152-0398","authenticated-orcid":false,"given":"Daniel","family":"Lea","sequence":"additional","affiliation":[{"name":"Advanced Data Analysis Centre, University of Nottingham, Sutton Bonington Campus, Sutton Bonington LE12 5RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Emes","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Sutton Bonington LE12 5RD, UK"},{"name":"Advanced Data Analysis Centre, University of Nottingham, Sutton Bonington Campus, Sutton Bonington LE12 5RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7733-906X","authenticated-orcid":false,"given":"Tania","family":"Dottorini","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Sutton Bonington LE12 5RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Pu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6602-7447","authenticated-orcid":false,"given":"Kin-Chow","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Sutton Bonington LE12 5RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11613","DOI":"10.1073\/pnas.1811345115","article-title":"The mechanism of resistance to favipiravir in influenza","volume":"115","author":"Goldhill","year":"2018","journal-title":"Proc. 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