Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation
A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified as the pathogen responsible for the outbreak of a severe, rapidly developing pneumonia (Coronavirus disease 2019, COVID-19). The virus enzyme, called 3CLpro or main protease (M<sup>pro</su...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9427 |
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| author | Simone Di Micco Simona Musella Marina Sala Maria C. Scala Graciela Andrei Robert Snoeck Giuseppe Bifulco Pietro Campiglia Alessio Fasano |
| author_facet | Simone Di Micco Simona Musella Marina Sala Maria C. Scala Graciela Andrei Robert Snoeck Giuseppe Bifulco Pietro Campiglia Alessio Fasano |
| author_sort | Simone Di Micco |
| collection | DOAJ |
| description | A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified as the pathogen responsible for the outbreak of a severe, rapidly developing pneumonia (Coronavirus disease 2019, COVID-19). The virus enzyme, called 3CLpro or main protease (M<sup>pro</sup>), is essential for viral replication, making it a most promising target for antiviral drug development. Recently, we adopted the drug repurposing as appropriate strategy to give fast response to global COVID-19 epidemic, by demonstrating that the zonulin octapeptide inhibitor AT1001 (Larazotide acetate) binds M<sup>pro</sup> catalytic domain. Thus, in the present study we tried to investigate the antiviral activity of AT1001, along with five derivatives, by cell-based assays. Our results provide with the identification of AT1001 peptide molecular framework for lead optimization step to develop new generations of antiviral agents of SARS-CoV-2 with an improved biological activity, expanding the chance for success in clinical trials. |
| first_indexed | 2024-03-10T08:10:47Z |
| format | Article |
| id | doaj.art-678541da66c04985b434378c71646ce4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:10:47Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-678541da66c04985b434378c71646ce42023-11-22T10:43:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012217942710.3390/ijms22179427Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity EvaluationSimone Di Micco0Simona Musella1Marina Sala2Maria C. Scala3Graciela Andrei4Robert Snoeck5Giuseppe Bifulco6Pietro Campiglia7Alessio Fasano8European Biomedical Research Institute of Salerno (EBRIS), Via Salvatore de Renzi 50, 84125 Salerno, ItalyEuropean Biomedical Research Institute of Salerno (EBRIS), Via Salvatore de Renzi 50, 84125 Salerno, ItalyDipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Salerno, ItalyDipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Salerno, ItalyDepartment of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, BelgiumDepartment of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, BelgiumDipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Salerno, ItalyDipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Salerno, ItalyEuropean Biomedical Research Institute of Salerno (EBRIS), Via Salvatore de Renzi 50, 84125 Salerno, ItalyA novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified as the pathogen responsible for the outbreak of a severe, rapidly developing pneumonia (Coronavirus disease 2019, COVID-19). The virus enzyme, called 3CLpro or main protease (M<sup>pro</sup>), is essential for viral replication, making it a most promising target for antiviral drug development. Recently, we adopted the drug repurposing as appropriate strategy to give fast response to global COVID-19 epidemic, by demonstrating that the zonulin octapeptide inhibitor AT1001 (Larazotide acetate) binds M<sup>pro</sup> catalytic domain. Thus, in the present study we tried to investigate the antiviral activity of AT1001, along with five derivatives, by cell-based assays. Our results provide with the identification of AT1001 peptide molecular framework for lead optimization step to develop new generations of antiviral agents of SARS-CoV-2 with an improved biological activity, expanding the chance for success in clinical trials.https://www.mdpi.com/1422-0067/22/17/9427SARS-CoV-2peptideFRETmolecular dockingmolecular dynamicsMM-GBSA |
| spellingShingle | Simone Di Micco Simona Musella Marina Sala Maria C. Scala Graciela Andrei Robert Snoeck Giuseppe Bifulco Pietro Campiglia Alessio Fasano Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation International Journal of Molecular Sciences SARS-CoV-2 peptide FRET molecular docking molecular dynamics MM-GBSA |
| title | Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation |
| title_full | Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation |
| title_fullStr | Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation |
| title_full_unstemmed | Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation |
| title_short | Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation |
| title_sort | peptide derivatives of the zonulin inhibitor larazotide at1001 as potential anti sars cov 2 molecular modelling synthesis and bioactivity evaluation |
| topic | SARS-CoV-2 peptide FRET molecular docking molecular dynamics MM-GBSA |
| url | https://www.mdpi.com/1422-0067/22/17/9427 |
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