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Given the absence of licensed antiviral therapies, the identification of effective small molecules remains critical. This study evaluated sixteen eugenol\u2010 and dihydroeugenol\u2010derived piperazine Mannich bases for antiviral activity against CHIKV, MAYV, and\n                    <jats:italic>Zika virus<\/jats:italic>\n                    (ZIKV) in Vero cells. Cytotoxicity was assessed using the MTT assay, and antiviral activity was quantified through median effective concentration (EC\n                    <jats:sub>50<\/jats:sub>\n                    ) and selectivity index (SI) values. Time\u2010dependent cytopathic effect inhibition, plaque reduction assays, virucidal assays and docking were performed to characterize the mechanism of action. Three compounds (\n                    <jats:bold>D3<\/jats:bold>\n                    ,\n                    <jats:bold>D7<\/jats:bold>\n                    , and\n                    <jats:bold>E7<\/jats:bold>\n                    ) exhibited selective antiviral activity. Notably, compound\n                    <jats:bold>D7<\/jats:bold>\n                    demonstrated low\u2010micromolar anti\u2010MAYV inhibition (EC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200914.43\u2009\u03bcM; SI\u2009&gt;\u200916.6), surpassing ribavirin by more than thirty\u2010fold in relative potency. Time\u2010dependent assays revealed progressive viral titer reductions of up to 3 log\n                    <jats:sub>10<\/jats:sub>\n                    PFU\/mL over 48\u2009h. Virucidal assays confirmed that\n                    <jats:bold>D7<\/jats:bold>\n                    does not directly inactivate viral particles. These findings identify\n                    <jats:bold>D7<\/jats:bold>\n                    as a promising antiviral lead compound and provide a foundation for further mechanistic, optimization, and in vivo studies aimed at developing anti\u2010alphavirus therapeutics.\n                  <\/jats:p>","DOI":"10.1002\/jmv.71158","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:16:43Z","timestamp":1789989403000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Eugenol\u2010Derived Piperazine Mannich Bases as Selective Inhibitors of Mayaro Virus: In Vitro Antiviral Evaluation and Mechanistic Insights"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7368-3573","authenticated-orcid":false,"given":"Adriana Cotta Cardoso","family":"Reis","sequence":"first","affiliation":[{"name":"Pharmacy School Federal University of Ouro Preto Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e1lia Lu\u00edza de Sousa da","family":"Silva","sequence":"additional","affiliation":[{"name":"Pharmacy School Federal University of Ouro Preto Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Portruneli","sequence":"additional","affiliation":[{"name":"Pharmacy School Federal University of Ouro Preto Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto Vieira Pontes","family":"Silva","sequence":"additional","affiliation":[{"name":"Pharmacy School Federal University of Ouro Preto Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3218-3107","authenticated-orcid":false,"given":"Saulo Fehelberg Pinto","family":"Braga","sequence":"additional","affiliation":[{"name":"Pharmacy School Federal University of Ouro Preto Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor Rodrigues","family":"Lapa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Federal University of Alfenas Alfenas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3627-6407","authenticated-orcid":false,"given":"Thiago Belarmino de","family":"Souza","sequence":"additional","affiliation":[{"name":"Pharmacy School Federal University of Ouro Preto Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Lopardi","family":"Franco","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Federal University of Alfenas Alfenas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6362-2822","authenticated-orcid":false,"given":"Diogo Teixeira","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Federal University of Alfenas Alfenas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7330-051X","authenticated-orcid":false,"given":"Geraldo C\u00e9lio","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"Pharmacy School Federal University of Ouro Preto Ouro Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-025-06314-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-018-3375-7"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens14050416"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.onehlt.2017.06.001"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-025-06761-8"},{"key":"e_1_2_10_7_1","unstructured":"P A H Organization. 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