In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study
Metal-based drugs represent a rich source of chemical substances of potential interest for the treatment of COVID-19. To this end, we have developed a small but representative panel of nine metal compounds, including both synthesized and commercially available complexes, suitable for medical applica...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/12/1858 |
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| author | Damiano Cirri Tiziano Marzo Iogann Tolbatov Alessandro Marrone Francesco Saladini Ilaria Vicenti Filippo Dragoni Adele Boccuto Luigi Messori |
| author_facet | Damiano Cirri Tiziano Marzo Iogann Tolbatov Alessandro Marrone Francesco Saladini Ilaria Vicenti Filippo Dragoni Adele Boccuto Luigi Messori |
| author_sort | Damiano Cirri |
| collection | DOAJ |
| description | Metal-based drugs represent a rich source of chemical substances of potential interest for the treatment of COVID-19. To this end, we have developed a small but representative panel of nine metal compounds, including both synthesized and commercially available complexes, suitable for medical application and tested them in vitro against the SARS-CoV-2 virus. The screening revealed that three compounds from the panel, i.e., the organogold(III) compound Aubipyc, the ruthenium(III) complex KP1019, and antimony trichloride (SbCl<sub>3</sub>), are endowed with notable antiviral properties and an acceptable cytotoxicity profile. These initial findings prompted us to perform a computational study to unveil the likely molecular basis of their antiviral actions. Calculations evidenced that the metalation of nucleophile sites in SARS-CoV-2 proteins or nucleobase strands, induced by Aubipyc, SbCl<sub>3</sub>, and KP1019, is likely to occur. Remarkably, we found that only the deprotonated forms of Cys and Sec residues can react favorably with these metallodrugs. The mechanistic implications of these findings are discussed. |
| first_indexed | 2024-03-10T04:33:12Z |
| format | Article |
| id | doaj.art-d845233acb5041cba0ec503d3f18e86b |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T04:33:12Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-d845233acb5041cba0ec503d3f18e86b2023-11-23T04:00:16ZengMDPI AGBiomolecules2218-273X2021-12-011112185810.3390/biom11121858In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational StudyDamiano Cirri0Tiziano Marzo1Iogann Tolbatov2Alessandro Marrone3Francesco Saladini4Ilaria Vicenti5Filippo Dragoni6Adele Boccuto7Luigi Messori8Laboratory of Metals in Medicine (MetMed), Department of Chemistry “U. Schiff”, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, ItalyDepartment of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126 Pisa, ItalyInstitut de Chimie Moleculaire de l’Université de Bourgogne (ICMUB), UMR CNRS 6302, Université de Bourgogne Franche-Comté (UBFC), Avenue Alain Savary 9, 21078 Dijon, FranceDipartimento di Farmacia, Università “G. d’Annunzio” Chieti-Pescara, Via dei Vestini, 66100 Chieti, ItalyDepartment of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, ItalyDepartment of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, ItalyDepartment of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, ItalyDepartment of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, ItalyDepartment of Chemistry and Industrial Chemistry (DCCI), University of Pisa, Via G. Moruzzi 13, 56124 Pisa, ItalyMetal-based drugs represent a rich source of chemical substances of potential interest for the treatment of COVID-19. To this end, we have developed a small but representative panel of nine metal compounds, including both synthesized and commercially available complexes, suitable for medical application and tested them in vitro against the SARS-CoV-2 virus. The screening revealed that three compounds from the panel, i.e., the organogold(III) compound Aubipyc, the ruthenium(III) complex KP1019, and antimony trichloride (SbCl<sub>3</sub>), are endowed with notable antiviral properties and an acceptable cytotoxicity profile. These initial findings prompted us to perform a computational study to unveil the likely molecular basis of their antiviral actions. Calculations evidenced that the metalation of nucleophile sites in SARS-CoV-2 proteins or nucleobase strands, induced by Aubipyc, SbCl<sub>3</sub>, and KP1019, is likely to occur. Remarkably, we found that only the deprotonated forms of Cys and Sec residues can react favorably with these metallodrugs. The mechanistic implications of these findings are discussed.https://www.mdpi.com/2218-273X/11/12/1858SARS-CoV-2COVID-19antiviral drugsmetallodrugsgoldruthenium |
| spellingShingle | Damiano Cirri Tiziano Marzo Iogann Tolbatov Alessandro Marrone Francesco Saladini Ilaria Vicenti Filippo Dragoni Adele Boccuto Luigi Messori In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study Biomolecules SARS-CoV-2 COVID-19 antiviral drugs metallodrugs gold ruthenium |
| title | In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study |
| title_full | In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study |
| title_fullStr | In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study |
| title_full_unstemmed | In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study |
| title_short | In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study |
| title_sort | in vitro anti sars cov 2 activity of selected metal compounds and potential molecular basis for their actions based on computational study |
| topic | SARS-CoV-2 COVID-19 antiviral drugs metallodrugs gold ruthenium |
| url | https://www.mdpi.com/2218-273X/11/12/1858 |
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