{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T12:22:38Z","timestamp":1774441358459,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordinaci\u00f3n de Investigaci\u00f3n en Salud (IMSS), and FUNDACI\u00d3N IMSS, A.C.\n\t\t\t\t\t\t\t\t              https:\/\/ror.org\/03xddgg98","award":["R-2024-785-073"],"award-info":[{"award-number":["R-2024-785-073"]}]},{"name":"SECIHTI","award":["CBF-2025-I-1331"],"award-info":[{"award-number":["CBF-2025-I-1331"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The continuous emergence of SARS-CoV-2 variants highlights the need for novel antiviral agents with favorable safety profiles. Marine microalgae constitute a valuable source of bioactive compounds, including antiviral peptides. Building on previous in silico identification of peptides derived from the marine microalga Phaeodactylum tricornutum with predicted activity against SARS-CoV-2, this study evaluated the antiviral capacity of peptide fractions generated by enzymatic hydrolysis and separated by molecular weight (10\u201330, 5\u201310, 3\u20135, and &lt;3 kDa) in human alveolar epithelial A549 cells infected with the SARS-CoV-2. Cytotoxicity analyses, assessed using MTT and resazurin assays, revealed a moderate, concentration-dependent reduction in metabolic activity while maintaining overall cell viability within an acceptable range for antiviral evaluation, with higher-molecular-weight fractions (10\u201330 and 5\u201310 kDa) displaying the most stable profiles. Antiviral activity was assessed by flow cytometry following post-infection treatment. Lower-molecular-weight fractions (3\u20135 and &lt;3 kDa) showed early reductions in infection at low concentrations but exhibited variable responses. In contrast, the 10\u201330 and 5\u201310 kDa fractions showed more robust, dose-dependent inhibition at medium and high concentrations, reducing infection levels to levels close to those observed in uninfected controls. Comparative analysis with the reference antiviral drug lopinavir demonstrated that peptide fractions exhibit lower cytotoxicity while retaining antiviral activity under equivalent experimental conditions. Overall, these results indicate that antiviral efficacy is strongly influenced by peptide molecular weight and consistency of response. This work provides experimental in vitro validation of P. tricornutum\u2013derived peptide fractions as marine antiviral candidates and supports the integration of in silico and functional approaches for marine drug discovery.<\/jats:p>","DOI":"10.3390\/md24040122","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:11:14Z","timestamp":1774429874000},"page":"122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Vitro Validation of Size-Dependent Antiviral Activity of Phaeodactylum tricornutum-Derived Peptide Fractions Against SARS-CoV-2"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8050-4587","authenticated-orcid":false,"given":"David Mauricio","family":"Ca\u00f1edo-Figueroa","sequence":"first","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"},{"name":"Laboratorio de Virolog\u00eda y Dise\u00f1o de Antivirales, Facultad de Medicina, Universidad Aut\u00f3noma de Sinaloa (UAS), Culiacan 80246, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8790-2341","authenticated-orcid":false,"given":"Blanca Azucena","family":"M\u00e1rquez-Reyna","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4853-3063","authenticated-orcid":false,"given":"Alan Orlando","family":"Santos-Mena","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela Nahomi","family":"Calder\u00f3n-Sandate","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flor Itzel","family":"Lira-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2124-2036","authenticated-orcid":false,"given":"Julio E.","family":"Casta\u00f1eda-Delgado","sequence":"additional","affiliation":[{"name":"Investigadores por M\u00e9xico (SECIHTI), Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto 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Virolog\u00eda Perinatal y Dise\u00f1o Molecular de Ant\u00edgenos y Biomarcadores, Departamento de Inmunobioquimica, Instituto Nacional de Perinatolog\u00eda \u201cIsidro Espinosa de los Reyes\u201d, Mexico City 11000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco Antonio","family":"Valdez-Flores","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Autonomous University of Sinaloa, Culiacan 80246, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"L\u00f3pez-Angulo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Autonomous University of Sinaloa, Culiacan 80246, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia Desire\u00e9","family":"Norzagaray-Valenzuela","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Autonomous University of Sinaloa, Culiacan 80246, 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