{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T06:22:39Z","timestamp":1790490159765,"version":"4.1.0"},"reference-count":32,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["204957\/Z\/16\/Z"],"award-info":[{"award-number":["204957\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["2R15GM116032-02A1"],"award-info":[{"award-number":["2R15GM116032-02A1"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008326","name":"Ball State University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008326","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In order to produce proteins essential for their propagation, many pathogenic human viruses, including SARS-CoV-2, the causative agent of COVID-19 respiratory disease, commandeer host biosynthetic machineries and mechanisms. Three major structural proteins, the spike, envelope and membrane proteins, are amongst several SARS-CoV-2 components synthesised at the endoplasmic reticulum (ER) of infected human cells prior to the assembly of new viral particles. Hence, the inhibition of membrane protein synthesis at the ER is an attractive strategy for reducing the pathogenicity of SARS-CoV-2 and other obligate viral pathogens. Using an in vitro system, we demonstrate that the small molecule inhibitor ipomoeassin F (Ipom-F) potently blocks the Sec61-mediated ER membrane translocation and\/or insertion of three therapeutic protein targets for SARS-CoV-2 infection; the viral spike and ORF8 proteins together with angiotensin-converting enzyme 2, the host cell plasma membrane receptor. Our findings highlight the potential for using ER protein translocation inhibitors such as Ipom-F as host-targeting, broad-spectrum antiviral agents.<\/jats:p>\n                  <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/jcs.257758","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T16:00:31Z","timestamp":1611072031000},"source":"Crossref","is-referenced-by-count":45,"title":["Ipomoeassin-F inhibits the\n                    <i>in vitro<\/i>\n                    biogenesis of the SARS-CoV-2 spike protein and its host cell membrane receptor"],"prefix":"10.1242","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1744-0198","authenticated-orcid":false,"given":"Sarah","family":"O'Keefe","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peristera","family":"Roboti","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwabena B.","family":"Duah","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ball State University, Muncie, IN 47306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7335-039X","authenticated-orcid":false,"given":"Guanghui","family":"Zong","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayden","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ball State University, Muncie, IN 47306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5453-1753","authenticated-orcid":false,"given":"Wei Q.","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ball State University, Muncie, IN 47306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4532-8152","authenticated-orcid":false,"given":"Stephen","family":"High","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,2,19]]},"reference":[{"key":"2021042623381237300_JCS257758C2","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/s41586-020-2332-7","article-title":"Proteomics of SARS-CoV-2 infected host cells reveals therapy targets","volume":"583","author":"Bojkova","year":"2020","journal-title":"Nature"},{"key":"2021042623381237300_JCS257758C3","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1126\/science.abd2985","article-title":"Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity","volume":"370","author":"Cantuti-Castelvetri","year":"2020","journal-title":"Science"},{"key":"2021042623381237300_JCS257758C4","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1016\/j.cell.2018.10.009","article-title":"EMC is required to initiate accurate membrane protein topogenesis","volume":"175","author":"Chitwood","year":"2018","journal-title":"Cell"},{"key":"2021042623381237300_JCS257758C5","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1126\/science.abd3072","article-title":"Neuropilin-1 is a host factor for SARS-CoV-2 infection","volume":"370","author":"Daly","year":"2020","journal-title":"Science"},{"key":"2021042623381237300_JCS257758C6","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s12860-020-00294-x","article-title":"Identification of a druggable binding pocket in the spike protein reveals a key site for existing drugs potentially capable of combating Covid-19 infectivity","volume":"21","author":"Drew","year":"2020","journal-title":"BMC Mol. 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