{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:16:38Z","timestamp":1760058998611,"version":"build-2065373602"},"reference-count":68,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005562","name":"North Carolina Biotechnology Center","doi-asserted-by":"publisher","award":["2021-FLG-3802"],"award-info":[{"award-number":["2021-FLG-3802"]}],"id":[{"id":"10.13039\/100005562","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The COVID-19 pandemic highlighted the need for new therapeutic strategies to counter emerging pathogenic viruses. Herein, we introduce a novel fusion protein platform that enables antiviral targeting of distinct viral species based on host receptor specificity. Proof-of-concept studies focused on the human coronavirus NL63, which shares specificity for the ACE2 host receptor with the pandemic SARS-CoV and SARS-CoV-2 species. This antiviral fusion protein combines IFN-\u03b2 with the soluble extracellular domain of ACE2 (IFN\u03b2-ACE2). Both domains retained predicted bioactivities in that the IFN-\u03b2 domain exhibited potent antiproliferative activity and the ACE2 domain exhibited full binding to the transmembrane SARS-CoV-2 Spike protein. In virus-washed (virus-targeted) and non-washed in vitro infection systems, we showed that the pool of IFN\u03b2-ACE2 targeted to the virion surface had superior antiviral activity against NL63 compared to soluble ACE2, IFN-\u03b2, or the unlinked combination of ACE2 and IFN-\u03b2. The pool of IFN\u03b2-ACE2 on the virion surface exhibited robust antiviral efficacy based on the preemptive targeting of antiviral IFN-\u03b2 activity to the proximal site of viral infection. In conclusion, virus-targeted IFN-\u03b2 places interferon optimally and antecedent to viral infection to constitute a new antiviral strategy.<\/jats:p>","DOI":"10.3390\/v17050697","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T09:26:48Z","timestamp":1747128408000},"page":"697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Antiviral Therapeutic Platform: Anchoring IFN-\u03b2 to the Surface of Infectious Virions Equips Interferon-Evasive Virions with Potent Antiviral Activity"],"prefix":"10.3390","volume":"17","author":[{"given":"Hoda H.","family":"Jabbour","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander G.","family":"Bastian","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayla B.","family":"DeOca","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0475-8516","authenticated-orcid":false,"given":"Mark D.","family":"Mannie","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/s41586-021-03291-y","article-title":"SARS-CoV-2 evolution during treatment of chronic infection","volume":"592","author":"Kemp","year":"2021","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1126\/science.371.6527.329","article-title":"New mutations raise specter of \u2019immune escape\u2019","volume":"371","author":"Kupferschmidt","year":"2021","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"eabg0821","DOI":"10.1126\/science.abg0821","article-title":"SARS-CoV-2 within-host diversity and transmission","volume":"372","author":"Lythgoe","year":"2021","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1126\/science.abf6950","article-title":"Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape","volume":"371","author":"McCarthy","year":"2021","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Triggle, C.R., Bansal, D., Ding, H., Islam, M.M., Farag, E., Hadi, H.A., and Sultan, A.A. 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