{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:31:24Z","timestamp":1787985084398,"version":"build-2784847793"},"reference-count":62,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro\u2014FAPERJ","award":["E-26\/211.058\/2021"],"award-info":[{"award-number":["E-26\/211.058\/2021"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro\u2014FAPERJ","award":["E-26\/210.124\/2021"],"award-info":[{"award-number":["E-26\/210.124\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>SARS-CoV-2, the causative agent of COVID-19, has led to over seven million deaths worldwide prior to May 2025. Despite widespread vaccination programs, COVID-19 remains a persistent global health challenge, underscoring the urgent need for new therapeutic approaches. Orientin is a flavonoid with reported antiviral activity, though its potential against SARS-CoV-2 remains poorly explored. This study aimed to investigate whether Orientin interacts with the viral Spike protein and impacts viral replication. Molecular docking simulations using DockThor were employed to predict the binding affinity between Orientin and the receptor-binding domain (RBD) of the Spike protein. Fluorescence spectroscopy assays were performed to assess direct interactions between Orientin and the trimeric form of the Spike protein. Additionally, cytotoxicity and viral replication assays were carried out in Vero cells to evaluate Orientin\u2019s antiviral effects. Docking results indicated that Orientin likely binds to key RBD residues involved in ACE2 receptor recognition. Spectroscopic analyses showed a decrease in intrinsic tryptophan fluorescence, suggesting direct interaction. Orientin demonstrated no cytotoxicity in Vero cells and exhibited moderate inhibition of viral replication. These findings suggest that Orientin interacts with critical regions of the Spike protein and may act as a moderate in vitro inhibitor of SARS-CoV-2, warranting further investigation into its therapeutic potential.<\/jats:p>","DOI":"10.3390\/v18010061","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:34:23Z","timestamp":1767198863000},"page":"61","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Interaction Between Orientin and the Spike of SARS-CoV-2: An In Silico and Experimental Approach"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7636-3708","authenticated-orcid":false,"given":"Gabriel Cavalcante","family":"Pacheco","sequence":"first","affiliation":[{"name":"N\u00facleo Multidisciplinar de Pesquisa em Biologia\u2014NUMPEX-BIO, Campus Duque de Caxias Professor Geraldo Cidade, Universidade Federal do Rio de Janeiro, Rio de Janeiro 25240-005, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3563-5228","authenticated-orcid":false,"given":"Michele de S\u00e1","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ultraestrutura Celular Herta Meyer, Centro de Pesquisa em Medicina de Precis\u00e3o, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-853, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2226-9938","authenticated-orcid":false,"given":"Camila Silva","family":"de Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"N\u00facleo Multidisciplinar de Pesquisa em Computa\u00e7\u00e3o\u2014Numpex-COMP, Campus Duque de Caxias Professor Geraldo Cidade, Universidade Federal do Rio de Janeiro, Rio de Janeiro 25240-005, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6584-4875","authenticated-orcid":false,"given":"Fabiana Avila","family":"Carneiro","sequence":"additional","affiliation":[{"name":"N\u00facleo Multidisciplinar de Pesquisa em Biologia\u2014NUMPEX-BIO, Campus Duque de Caxias Professor Geraldo Cidade, Universidade Federal do Rio de Janeiro, Rio de Janeiro 25240-005, Brazil"},{"name":"Laborat\u00f3rio de Ultraestrutura Celular Herta Meyer, Centro de Pesquisa em Medicina de Precis\u00e3o, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-853, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"fuaa057","DOI":"10.1093\/femsre\/fuaa057","article-title":"Molecular Diversity of Coronavirus Host Cell Entry Receptors","volume":"45","author":"Millet","year":"2020","journal-title":"FEMS Microbiol. 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