{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T02:14:40Z","timestamp":1783131280385,"version":"3.54.6"},"reference-count":67,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"crossref","award":["APQ-00038-22"],"award-info":[{"award-number":["APQ-00038-22"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"crossref","award":["BPD-00023-22"],"award-info":[{"award-number":["BPD-00023-22"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Inova Fiocruz Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Despite the availability of effective vaccines, yellow fever outbreaks persist, highlighting the need for antiviral drugs. Background\/Objectives: This study investigated Hippeastrum puniceum (Amaryllidaceae) as a potential source of antiviral compounds against wild-type yellow fever virus (wt-YFV). Methods\/Results: The crude bulb extract of H. puniceum exhibited 58% protection against wt-YFV. Bioassay-guided fractionation of the extract by UHPLC-HRMS led to the annotation of six alkaloids (bulbisine, cathinone, trigonelline, tetrahydroharman-3-carboxylic acid, and 2,7-dimethoxyhomolycorine or 3-O-acetylnarcissidine) in active fractions, along with the amino acids arginine, asparagine, tryptophan, and glutamic acid. In silico ADMET analyses predicted favorable pharmacokinetic and toxicological profiles, supporting their potential as drug candidates. Six of the annotated compounds were evaluated in vitro for cytotoxicity and antiviral activity against wt-YFV. However, none showed significant antiviral activity when tested individually, suggesting that the observed antiviral effect may result from synergistic interactions between two or more compounds within active fractions. Conclusions: Our results underscore the importance of further investigations in vitro, particularly assays exploring the synergy among the annotated compounds against YFV. The integration of bioassay-guided fractionation of active plant extracts with computational analyses emerges as a promising strategy for the discovery of natural products with therapeutic potential against yellow fever, a reemerging disease.<\/jats:p>","DOI":"10.3390\/molecules30214149","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T02:03:48Z","timestamp":1761185028000},"page":"4149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Potential Antiviral Compounds from Hippeastrum puniceum Bulb Against Yellow Fever Virus: Bioassay-Guided Fractionation and In Silico Pharmacokinetic Analysis"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6548-147X","authenticated-orcid":false,"given":"Eliza","family":"Flores-Souza","sequence":"first","affiliation":[{"name":"Grupo de Pesquisa em Imunologia Celular e Molecular, Instituto Ren\u00e9 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Celular e Molecular, Instituto Ren\u00e9 Rachou-Fiocruz Minas, Belo Horizonte 30190-002, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1871-9860","authenticated-orcid":false,"given":"Tha\u00eds Magalh\u00e3es","family":"Ac\u00e1cio","sequence":"additional","affiliation":[{"name":"Grupo de Pesquisa de Qu\u00edmica de Produtos Naturais Bioativos, Instituto Ren\u00e9 Rachou-Fiocruz Minas, Belo Horizonte 30190-002, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3210-7342","authenticated-orcid":false,"given":"Emerson de Castro","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Grupo de Pesquisa em Imunologia Celular e Molecular, Instituto Ren\u00e9 Rachou-Fiocruz Minas, Belo Horizonte 30190-002, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naiara Clemente","family":"Tavares","sequence":"additional","affiliation":[{"name":"Grupo de Pesquisa em Imunologia Celular e Molecular, Instituto Ren\u00e9 Rachou-Fiocruz Minas, Belo Horizonte 30190-002, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1406-6401","authenticated-orcid":false,"given":"Carlos Eduardo","family":"Calzavara-Silva","sequence":"additional","affiliation":[{"name":"Grupo de Pesquisa em Imunologia Celular e Molecular, Instituto Ren\u00e9 Rachou-Fiocruz Minas, Belo Horizonte 30190-002, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1859-177X","authenticated-orcid":false,"given":"Carlos Leomar","family":"Zani","sequence":"additional","affiliation":[{"name":"Grupo de Pesquisa de Qu\u00edmica de Produtos Naturais Bioativos, Instituto Ren\u00e9 Rachou-Fiocruz Minas, Belo Horizonte 30190-002, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3004-2119","authenticated-orcid":false,"given":"Douglas Eduardo Valente","family":"Pires","sequence":"additional","affiliation":[{"name":"School of Computing and Information Systems, The University of Melbourne, Melbourne 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0582-3968","authenticated-orcid":false,"given":"T\u00e2nia Maria de Almeida","family":"Alves","sequence":"additional","affiliation":[{"name":"Grupo de Pesquisa de Qu\u00edmica de Produtos Naturais Bioativos, Instituto Ren\u00e9 Rachou-Fiocruz Minas, Belo Horizonte 30190-002, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0487-8748","authenticated-orcid":false,"given":"Jaquelline Germano","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Grupo de Pesquisa em Imunologia Celular e 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