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To continue to uncover natural products (NPs) that can inhibit validated biochemical targets of coronaviruses, we focused on a subset of brown algae extracts from Puerto Rico that demonstrated potential anti\u2010SARS\u2010CoV\u20102 activity through selective disruption of the viral Spike\u2010receptor binding domain (RBD) to the host angiotensin\u2010converting enzyme\u20102 (ACE2) cellular entry receptor, which in turn led to further evaluation of a\n                    <jats:italic>Lobophora variegata<\/jats:italic>\n                    organic extract. Employing bioassay\u2010guided fractionation and modern NPs dereplication tools, we quickly identified fucoxanthin as an active constituent with selective inhibitory activity against spike\u2010RBD\/ACE\u20102 binding while also exhibiting moderate potency in vitro toward pseudo\u2010virus\u2010infected VERO cells. Preliminary in silico docking demonstrated that fucoxanthin binds stably at the RBD\u2010spike protein interface and has provided a hypothesized binding site for further chemical and biological studies.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202501403","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T19:02:06Z","timestamp":1756494126000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioassay\u2010guided Isolation of SARS\u2010CoV\u20102 Viral Entry Inhibitors From the Brown Algae\n                    <i>Lobophora variegata<\/i>\n                    Identifies Fucoxanthin as a Selective ACE\u20102\/Spike Inhibitor"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8244-4662","authenticated-orcid":false,"given":"Victoria M.","family":"Casimir\u2010Mont\u00e1n","sequence":"first","affiliation":[{"name":"Department of Chemistry, Natural Sciences College University of Puerto Rico \u2010 Rio Piedras Campus  San Juan Puerto Rico USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0332-0942","authenticated-orcid":false,"given":"Marie L.","family":"Matos\u2010Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy University of Puerto Rico \u2010 Medical Sciences Campus  San Juan Puerto Rico USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adri\u00e1n","family":"Gonz\u00e1lez\u2010Bravo","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program, Natural Sciences College University of Puerto Rico \u2013 Rio Piedras Campus  San Juan Puerto Rico USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5504-2545","authenticated-orcid":false,"given":"Edwin A.","family":"Hern\u00e1ndez\u2010Delgado","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program, Natural Sciences College University of Puerto Rico \u2013 Rio Piedras Campus  San Juan Puerto Rico USA"},{"name":"Department of Environmental Sciences, Natural Sciences College University of Puerto Rico \u2013 Rio Piedras Campus  San Juan Puerto Rico USA"},{"name":"Center For Applied Tropical Ecology and Conservation University of Puerto Rico \u2013 Rio Piedras Campus  San Juan Puerto Rico USA"},{"name":"Sociedad Ambiente Marino  San Juan Puerto Rico USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8309-1487","authenticated-orcid":false,"given":"Grayce","family":"Dyer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy University of Puerto Rico \u2010 Medical Sciences Campus  San Juan Puerto Rico USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2184-5980","authenticated-orcid":false,"given":"Joseph M.","family":"Salvino","sequence":"additional","affiliation":[{"name":"The Wistar Institute  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis J.","family":"Montaner","sequence":"additional","affiliation":[{"name":"The Wistar Institute  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel A.","family":"Cassel","sequence":"additional","affiliation":[{"name":"The Wistar Institute  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Troy E.","family":"Messick","sequence":"additional","affiliation":[{"name":"The Wistar Institute  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8991-6490","authenticated-orcid":false,"given":"Ian","family":"Tietjen","sequence":"additional","affiliation":[{"name":"The Wistar Institute  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2049-6248","authenticated-orcid":false,"given":"Eduardo J. 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