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Therefore, carbohydrate binding agents may represent potential candidates to abrogate virus infection. Here, we evaluated the in vitro anti-SARS-CoV-2 activity of two mannose-binding lectins isolated from the Brazilian plants Canavalia brasiliensis and Dioclea violacea (ConBR and DVL). These lectins inhibited SARS-CoV-2 Wuhan-Hu-1 strain and variants Gamma and Omicron infections, with selectivity indexes (SI) of 7, 1.7, and 6.5, respectively for ConBR; and 25, 16.8, and 22.3, for DVL. ConBR and DVL inhibited over 95% of the early stages of the viral infection, with strong virucidal effect, and also protected cells from infection and presented post-entry inhibition. The presence of mannose resulted in the complete lack of anti-SARS-CoV-2 activity by ConBR and DVL, recovering virus titers. ATR-FTIR, molecular docking, and dynamic simulation between SARS-CoV-2 S and either lectins indicated molecular interactions with predicted binding energies of \u221285.4 and \u221272.0 Kcal\/Mol, respectively. Our findings show that ConBR and DVL lectins possess strong activities against SARS-CoV-2, potentially by interacting with glycans and blocking virus entry into cells, representing potential candidates for the development of novel antiviral drugs.<\/jats:p>","DOI":"10.3390\/v15091886","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T10:14:14Z","timestamp":1693995254000},"page":"1886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Mannose-Binding Lectins as Potent Antivirals against SARS-CoV-2"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7313-1261","authenticated-orcid":false,"given":"Vict\u00f3ria Riquena","family":"Grosche","sequence":"first","affiliation":[{"name":"Laboratory of Antiviral Research, Institute of Biomedical Science (ICBIM), Federal University of Uberl\u00e2ndia (UFU), Uberl\u00e2ndia 38405-317, 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