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In this context, medicinal plants became accessible alternatives for symptom management and disease prevention, highlighting the value of traditional health systems as sources of biologically relevant species for further investigation. This study documented medicinal plants used to prevent and treat COVID-19 in S\u00e3o Lu\u00eds, Maranh\u00e3o, Brazil, and evaluated the inhibitory activity of Uncaria tomentosa (Willd. Ex Schult)extracts, the most frequently cited species, against the SARS-CoV-2 RBD:ACE2 interaction. An ethnopharmacological survey was initially conducted with 400 participants between November 2022 and March 2023 where a total of 38 medicinal ethnospecies were reported, with an overall prevalence of medicinal plant use of 22.75%. Considering that aqueous preparations were the predominant form of use reported by participants, both aqueous and ethanolic extracts were prepared from the stem bark and leaves of U. tomentosa and evaluated in an in vitro Spike (RBD) inhibition assay. The highest inhibitory activity was observed for stem bark extracts of U. tomentosa, which achieved 98.09% inhibition for the ethanolic extract and 73.40% for the aqueous extract. Preparations obtained from the leaves showed lower activity, with inhibition values of 41.12% and 19.74%, respectively. Chemical profiling was performed by LC-MS\/MS combined with molecular networking. Chemical analysis enabled the annotation of oxindole alkaloids and flavonoids previously reported in the literature as exhibiting relevant biological activities in models of viral infections. These findings highlight the ethnopharmacological relevance of U. tomentosa, support its potential as a source of bioactive metabolites, and reinforce the value of ethnopharmacological approaches in identifying promising species for further biological investigation.<\/jats:p>","DOI":"10.3390\/plants15131998","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:16:44Z","timestamp":1782699404000},"page":"1998","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Traditional Knowledge to SARS-CoV-2 Entry Inhibitor Metabolites: Ethnopharmacological Investigation of Uncaria tomentosa (Willd. ex Schult.) DC"],"prefix":"10.3390","volume":"15","author":[{"given":"Beatriz Ribeiro","family":"Ferreira","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biotecnologia Vegetal e Bioprocessos, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"},{"name":"Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Freire","family":"Campos","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Beatriz F.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Departamento de Farm\u00e1cia, Universidade Federal do Maranh\u00e3o, Campus Bacanga, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Beatriz","family":"Lima","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simony Carvalho","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8502-1625","authenticated-orcid":false,"given":"Cris\u00e1lida M.","family":"Vilanova","sequence":"additional","affiliation":[{"name":"Departamento de Farm\u00e1cia, Universidade Federal do Maranh\u00e3o, Campus Bacanga, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5665-9280","authenticated-orcid":false,"given":"Denise F.","family":"Coutinho","sequence":"additional","affiliation":[{"name":"Departamento de Farm\u00e1cia, Universidade Federal do Maranh\u00e3o, Campus Bacanga, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1410-480X","authenticated-orcid":false,"given":"Diego","family":"Allonso","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7845-8562","authenticated-orcid":false,"given":"Flavia Maria M.","family":"Amaral","sequence":"additional","affiliation":[{"name":"Departamento de Farm\u00e1cia, Universidade Federal do Maranh\u00e3o, Campus Bacanga, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7445-074X","authenticated-orcid":false,"given":"Suzana Guimar\u00e3es","family":"Leit\u00e3o","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biotecnologia Vegetal e Bioprocessos, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"},{"name":"Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1056\/NEJMoa2007764","article-title":"Remdesivir for the Treatment of Covid-19\u2014Final Report","volume":"383","author":"Beigel","year":"2020","journal-title":"N. 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