Marine-Derived Peptides from <i>Phaeodactylum tricornutum</i> as Potential SARS-CoV-2 Mpro Inhibitors: An <i>In Silico</i> Approach
The ongoing threat of viral pandemics such as COVID-19 highlights the urgent need for novel antiviral therapeutics targeting conserved viral proteins. In this study, peptides of 10–30 kDa derived from the marine diatom <i>Phaeodactylum tricornutum</i> were identified as potential inhibit...
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2025-05-01
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| author | David Mauricio Cañedo-Figueroa Marco Antonio Valdez-Flores Claudia Desireé Norzagaray-Valenzuela Loranda Calderón-Zamora Ángel Radamés Rábago-Monzón Josué Camberos-Barraza Alma Marlene Guadrón-Llanos Alberto Kousuke De la Herrán-Arita Verónica Judith Picos-Cárdenas Alejandro Camacho-Zamora Alejandra Romero-Utrilla Carlos Daniel Cordero-Rivera Rosa María del Ángel Moisés León-Juárez José Manuel Reyes-Ruiz Carlos Noe Farfan-Morales Luis Adrián De Jesús-González Juan Fidel Osuna-Ramos |
| author_facet | David Mauricio Cañedo-Figueroa Marco Antonio Valdez-Flores Claudia Desireé Norzagaray-Valenzuela Loranda Calderón-Zamora Ángel Radamés Rábago-Monzón Josué Camberos-Barraza Alma Marlene Guadrón-Llanos Alberto Kousuke De la Herrán-Arita Verónica Judith Picos-Cárdenas Alejandro Camacho-Zamora Alejandra Romero-Utrilla Carlos Daniel Cordero-Rivera Rosa María del Ángel Moisés León-Juárez José Manuel Reyes-Ruiz Carlos Noe Farfan-Morales Luis Adrián De Jesús-González Juan Fidel Osuna-Ramos |
| author_sort | David Mauricio Cañedo-Figueroa |
| collection | DOAJ |
| description | The ongoing threat of viral pandemics such as COVID-19 highlights the urgent need for novel antiviral therapeutics targeting conserved viral proteins. In this study, peptides of 10–30 kDa derived from the marine diatom <i>Phaeodactylum tricornutum</i> were identified as potential inhibitors of SARS-CoV-2 main protease (Mpro), a key enzyme in viral replication. Peptides less than 60 amino acids in length were retrieved from the UniProt database and aligned with reference antiviral sequences using the Biopython pairwise2 algorithm. Six candidates were selected for structural modeling using AlphaFold2 and Swiss-Model, followed by molecular docking using ClusPro2. LigPlot+ was used to assess molecular interactions, while NetMHCpan 4.1 and AVPpred evaluated immunogenicity and antiviral potential, respectively. Molecular dynamics simulations over 100 ns were conducted using OpenMM. These peptides demonstrated stable binding interactions with key catalytic residues of Mpro. Specifically, peptide A0A8J9SA87 interacted with Cys145 and Glu166, while peptide A0A8J9SDW0 exhibited interactions with His41 and Phe140, both of which are known to be essential for Mpro inhibition. Although peptide A0A8J9X3P8 also interacted with catalytic residues, it exhibited greater structural fluctuations during molecular dynamics simulations and achieved lower AVPpred scores, suggesting lower overall antiviral potential. Therefore, A0A8J9SA87 and A0A8J9SDW0 were identified as the most promising candidates. Molecular dynamics simulations further supported the high structural stability of these peptide-Mpro complexes over a 100 ns timescale, reinforcing their potential as effective inhibitors. These findings support <i>P. tricornutum</i> as a valuable source of antiviral peptides and demonstrate the feasibility of <i>in silico</i> pipelines for identifying therapeutic candidates against SARS-CoV-2. |
| format | Article |
| id | doaj-art-49744afcf5cd40bca7922e8b581db3cd |
| institution | OA Journals |
| issn | 2076-2607 |
| language | English |
| publishDate | 2025-05-01 |
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| series | Microorganisms |
| spelling | doaj-art-49744afcf5cd40bca7922e8b581db3cd2025-08-20T02:21:07ZengMDPI AGMicroorganisms2076-26072025-05-01136127110.3390/microorganisms13061271Marine-Derived Peptides from <i>Phaeodactylum tricornutum</i> as Potential SARS-CoV-2 Mpro Inhibitors: An <i>In Silico</i> ApproachDavid Mauricio Cañedo-Figueroa0Marco Antonio Valdez-Flores1Claudia Desireé Norzagaray-Valenzuela2Loranda Calderón-Zamora3Ángel Radamés Rábago-Monzón4Josué Camberos-Barraza5Alma Marlene Guadrón-Llanos6Alberto Kousuke De la Herrán-Arita7Verónica Judith Picos-Cárdenas8Alejandro Camacho-Zamora9Alejandra Romero-Utrilla10Carlos Daniel Cordero-Rivera11Rosa María del Ángel12Moisés León-Juárez13José Manuel Reyes-Ruiz14Carlos Noe Farfan-Morales15Luis Adrián De Jesús-González16Juan Fidel Osuna-Ramos17Faculty of Medicine, Autonomous University of Sinaloa, Culiacán 80246, MexicoFaculty of Medicine, Autonomous University of Sinaloa, Culiacán 80246, MexicoFaculty of Biology, Autonomous University of Sinaloa, Culiacán 80019, MexicoFaculty of Biology, Autonomous University of Sinaloa, Culiacán 80019, MexicoFaculty of Medicine, Autonomous University of Sinaloa, Culiacán 80246, MexicoFaculty of Medicine, Autonomous University of Sinaloa, Culiacán 80246, MexicoFaculty of Medicine, Autonomous University of Sinaloa, Culiacán 80246, MexicoFaculty of Medicine, Autonomous University of Sinaloa, Culiacán 80246, MexicoFaculty of Medicine, Autonomous University of Sinaloa, Culiacán 80246, MexicoFaculty of Medicine, Autonomous University of Sinaloa, Culiacán 80246, MexicoDepartamento de Anatomía Patológica, Instituto Mexicano del Seguro Social (IMSS), Culiacán 80200, MexicoDepartment of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City 07360, MexicoDepartment of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City 07360, MexicoLaboratorio de Virología Perinatal y Diseño Molecular de Antígenos y Biomarcadores, Departamento de Inmunobioquímica, Instituto Nacional de Perinatología, Ciudad de México 11000, MexicoUnidad Médica de Alta Especialidad, Hospital de Especialidades No. 14, Centro Médico Nacional “Adolfo Ruiz Cortines”, Instituto Mexicano del Seguro Social (IMSS), Veracruz 91897, MexicoDepartamento de Ciencias Naturales, Universidad Autónoma Metropolitana (UAM), Unidad Cuajimalpa, Ciudad de México 05348, MexicoUnidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, MexicoFaculty of Medicine, Autonomous University of Sinaloa, Culiacán 80246, MexicoThe ongoing threat of viral pandemics such as COVID-19 highlights the urgent need for novel antiviral therapeutics targeting conserved viral proteins. In this study, peptides of 10–30 kDa derived from the marine diatom <i>Phaeodactylum tricornutum</i> were identified as potential inhibitors of SARS-CoV-2 main protease (Mpro), a key enzyme in viral replication. Peptides less than 60 amino acids in length were retrieved from the UniProt database and aligned with reference antiviral sequences using the Biopython pairwise2 algorithm. Six candidates were selected for structural modeling using AlphaFold2 and Swiss-Model, followed by molecular docking using ClusPro2. LigPlot+ was used to assess molecular interactions, while NetMHCpan 4.1 and AVPpred evaluated immunogenicity and antiviral potential, respectively. Molecular dynamics simulations over 100 ns were conducted using OpenMM. These peptides demonstrated stable binding interactions with key catalytic residues of Mpro. Specifically, peptide A0A8J9SA87 interacted with Cys145 and Glu166, while peptide A0A8J9SDW0 exhibited interactions with His41 and Phe140, both of which are known to be essential for Mpro inhibition. Although peptide A0A8J9X3P8 also interacted with catalytic residues, it exhibited greater structural fluctuations during molecular dynamics simulations and achieved lower AVPpred scores, suggesting lower overall antiviral potential. Therefore, A0A8J9SA87 and A0A8J9SDW0 were identified as the most promising candidates. Molecular dynamics simulations further supported the high structural stability of these peptide-Mpro complexes over a 100 ns timescale, reinforcing their potential as effective inhibitors. These findings support <i>P. tricornutum</i> as a valuable source of antiviral peptides and demonstrate the feasibility of <i>in silico</i> pipelines for identifying therapeutic candidates against SARS-CoV-2.https://www.mdpi.com/2076-2607/13/6/1271antiviral peptidesSARS-CoV-2main protease (Mpro)<i>Phaeodactylum tricornutum</i><i>in silico</i> analysis |
| spellingShingle | David Mauricio Cañedo-Figueroa Marco Antonio Valdez-Flores Claudia Desireé Norzagaray-Valenzuela Loranda Calderón-Zamora Ángel Radamés Rábago-Monzón Josué Camberos-Barraza Alma Marlene Guadrón-Llanos Alberto Kousuke De la Herrán-Arita Verónica Judith Picos-Cárdenas Alejandro Camacho-Zamora Alejandra Romero-Utrilla Carlos Daniel Cordero-Rivera Rosa María del Ángel Moisés León-Juárez José Manuel Reyes-Ruiz Carlos Noe Farfan-Morales Luis Adrián De Jesús-González Juan Fidel Osuna-Ramos Marine-Derived Peptides from <i>Phaeodactylum tricornutum</i> as Potential SARS-CoV-2 Mpro Inhibitors: An <i>In Silico</i> Approach Microorganisms antiviral peptides SARS-CoV-2 main protease (Mpro) <i>Phaeodactylum tricornutum</i> <i>in silico</i> analysis |
| title | Marine-Derived Peptides from <i>Phaeodactylum tricornutum</i> as Potential SARS-CoV-2 Mpro Inhibitors: An <i>In Silico</i> Approach |
| title_full | Marine-Derived Peptides from <i>Phaeodactylum tricornutum</i> as Potential SARS-CoV-2 Mpro Inhibitors: An <i>In Silico</i> Approach |
| title_fullStr | Marine-Derived Peptides from <i>Phaeodactylum tricornutum</i> as Potential SARS-CoV-2 Mpro Inhibitors: An <i>In Silico</i> Approach |
| title_full_unstemmed | Marine-Derived Peptides from <i>Phaeodactylum tricornutum</i> as Potential SARS-CoV-2 Mpro Inhibitors: An <i>In Silico</i> Approach |
| title_short | Marine-Derived Peptides from <i>Phaeodactylum tricornutum</i> as Potential SARS-CoV-2 Mpro Inhibitors: An <i>In Silico</i> Approach |
| title_sort | marine derived peptides from i phaeodactylum tricornutum i as potential sars cov 2 mpro inhibitors an i in silico i approach |
| topic | antiviral peptides SARS-CoV-2 main protease (Mpro) <i>Phaeodactylum tricornutum</i> <i>in silico</i> analysis |
| url | https://www.mdpi.com/2076-2607/13/6/1271 |
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