{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T17:44:19Z","timestamp":1778262259456,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82161138002 and 92169112 to S.J.; 82002142 to S.X."],"award-info":[{"award-number":["82161138002 and 92169112 to S.J.; 82002142 to S.X."]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the National Key Research and Development Program of China","award":["2021YFC2300703 to L.L."],"award-info":[{"award-number":["2021YFC2300703 to L.L."]}]},{"name":"the Program of Shanghai Aca-demic\/Technology Research Leader","award":["20XD1420300 to L.L."],"award-info":[{"award-number":["20XD1420300 to L.L."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The coronavirus disease 2019 (COVID-19) pandemic caused by infection of SARS-CoV-2 and its variants has posed serious threats to global public health, thus calling for the development of potent and broad-spectrum antivirals. We previously designed and developed a peptide-based pan-coronavirus (CoV) fusion inhibitor, EK1, which is effective against all human CoVs (HCoV) tested by targeting the HCoV S protein HR1 domain. However, its relatively short half-life may limit its clinical use. Therefore, we designed, constructed, and expressed a recombinant protein, FL-EK1, which consists of a modified fibronectin type III domain (FN3) with albumin-binding capacity, a flexible linker, and EK1. As with EK1, we found that FL-EK1 could also effectively inhibit infection of SARS-CoV-2 and its variants, as well as HCoV-OC43. Furthermore, it protected mice from infection by the SARS-CoV-2 Delta variant and HCoV-OC43. Importantly, the half-life of FL-EK1 (30 h) is about 15.7-fold longer than that of EK1 (1.8 h). These results suggest that FL-EK1 is a promising candidate for the development of a pan-CoV fusion inhibitor-based long-acting antiviral drug for preventing and treating infection by current and future SARS-CoV-2 variants, as well as other HCoVs.<\/jats:p>","DOI":"10.3390\/v14040655","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T23:20:55Z","timestamp":1647991255000},"page":"655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Modified Fibronectin Type III Domain-Conjugated, Long-Acting Pan-Coronavirus Fusion Inhibitor with Extended Half-Life"],"prefix":"10.3390","volume":"14","author":[{"given":"Qianyu","family":"Duan","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Xia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanke","family":"Jiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5322-0283","authenticated-orcid":false,"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Prosperous Biopharm Company, Beijing 100021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2255-0391","authenticated-orcid":false,"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8283-7135","authenticated-orcid":false,"given":"Shibo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1128\/JVI.06540-11","article-title":"Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus","volume":"86","author":"Woo","year":"2012","journal-title":"J. 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