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Despite the growing need for medical intervention, no FDA-approved vaccines are yet available, and treatment has been limited to supportive therapy for the alleviation of symptoms. Entry inhibitors could fill the important role of preventing initial infection and preventing spread. Here, we describe the design, synthesis, and evaluation of a lipopeptide that is derived from the HRC domain of the SARS-CoV-2 S glycoprotein that potently inhibits fusion mediated by SARS-CoV-2 S glycoprotein and blocks infection by live SARS-CoV-2 in both cell monolayers (\n            <jats:italic>in vitro<\/jats:italic>\n            ) and human airway tissues (\n            <jats:italic>ex vivo<\/jats:italic>\n            ). Our results highlight the SARS-CoV-2 HRC-derived lipopeptide as a promising therapeutic candidate for SARS-CoV-2 infections.\n          <\/jats:p>","DOI":"10.1128\/mbio.01935-20","type":"journal-article","created":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T15:39:15Z","timestamp":1603121955000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":79,"title":["Inhibition of Coronavirus Entry\n            <i>In Vitro<\/i>\n            and\n            <i>Ex Vivo<\/i>\n            by a Lipid-Conjugated Peptide Derived from the SARS-CoV-2 Spike Glycoprotein HRC Domain"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7054-4204","authenticated-orcid":false,"given":"Victor K.","family":"Outlaw","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Wisconsin, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca T.","family":"Bovier","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Columbia University Medical Center, New York, New York, USA"},{"name":"Center for Host-Pathogen Interaction, Columbia University Medical Center, New York, New York, USA"},{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli,\u201d Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan C.","family":"Mears","sequence":"additional","affiliation":[{"name":"Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Department of Experimental Pathology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria N.","family":"Cajimat","sequence":"additional","affiliation":[{"name":"Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Department of Experimental Pathology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Columbia University Medical Center, New York, New York, USA"},{"name":"Center for Host-Pathogen Interaction, Columbia University Medical Center, New York, New York, USA"},{"name":"Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle J.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Addetia","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole A. 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