In Silico Multi-Target Approach Revealed Potential Lead Compounds as Scaffold for the Synthesis of Chemical Analogues Targeting SARS-CoV-2
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), an infectious disease that spreads rapidly in humans. In March 2020, the World Health Organization (WHO) declared a COVID-19 pandemic. Identifying a multi-target-directed ligand approach would op...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/11/3/465 |
| _version_ | 1797472768909901824 |
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| author | Alfonso Trezza Claudia Mugnaini Federico Corelli Annalisa Santucci Ottavia Spiga |
| author_facet | Alfonso Trezza Claudia Mugnaini Federico Corelli Annalisa Santucci Ottavia Spiga |
| author_sort | Alfonso Trezza |
| collection | DOAJ |
| description | Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), an infectious disease that spreads rapidly in humans. In March 2020, the World Health Organization (WHO) declared a COVID-19 pandemic. Identifying a multi-target-directed ligand approach would open up new opportunities for drug discovery to combat COVID-19. The aim of this work was to perform a virtual screening of an exclusive chemical library of about 1700 molecules containing both pharmacologically active compounds and synthetic intermediates to propose potential protein inhibitors for use against SARS-CoV-2. In silico analysis showed that our compounds triggered an interaction network with key residues of the SARS-CoV-2 spike protein (S-protein), blocking trimer formation and interaction with the human receptor hACE2, as well as with the main 3C-like protease (3CLpro), inhibiting their biological function. Our data may represent a step forward in the search for potential new chemotherapeutic agents for the treatment of COVID-19. |
| first_indexed | 2024-03-09T20:05:56Z |
| format | Article |
| id | doaj.art-898ddf1478c3407eb4c329c97715f1d9 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T20:05:56Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-898ddf1478c3407eb4c329c97715f1d92023-11-24T00:31:12ZengMDPI AGBiology2079-77372022-03-0111346510.3390/biology11030465In Silico Multi-Target Approach Revealed Potential Lead Compounds as Scaffold for the Synthesis of Chemical Analogues Targeting SARS-CoV-2Alfonso Trezza0Claudia Mugnaini1Federico Corelli2Annalisa Santucci3Ottavia Spiga4Department of Biotechnology, Chemistry and Pharmacy (Department of Excellence 2018–2022), University of Siena, 53100 Siena, ItalyDepartment of Biotechnology, Chemistry and Pharmacy (Department of Excellence 2018–2022), University of Siena, 53100 Siena, ItalyDepartment of Biotechnology, Chemistry and Pharmacy (Department of Excellence 2018–2022), University of Siena, 53100 Siena, ItalyDepartment of Biotechnology, Chemistry and Pharmacy (Department of Excellence 2018–2022), University of Siena, 53100 Siena, ItalyDepartment of Biotechnology, Chemistry and Pharmacy (Department of Excellence 2018–2022), University of Siena, 53100 Siena, ItalySevere acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), an infectious disease that spreads rapidly in humans. In March 2020, the World Health Organization (WHO) declared a COVID-19 pandemic. Identifying a multi-target-directed ligand approach would open up new opportunities for drug discovery to combat COVID-19. The aim of this work was to perform a virtual screening of an exclusive chemical library of about 1700 molecules containing both pharmacologically active compounds and synthetic intermediates to propose potential protein inhibitors for use against SARS-CoV-2. In silico analysis showed that our compounds triggered an interaction network with key residues of the SARS-CoV-2 spike protein (S-protein), blocking trimer formation and interaction with the human receptor hACE2, as well as with the main 3C-like protease (3CLpro), inhibiting their biological function. Our data may represent a step forward in the search for potential new chemotherapeutic agents for the treatment of COVID-19.https://www.mdpi.com/2079-7737/11/3/465docking simulationSARS-CoV-2 spike protein3CLproCOVID-19multi-target inhibitorshomology modeling |
| spellingShingle | Alfonso Trezza Claudia Mugnaini Federico Corelli Annalisa Santucci Ottavia Spiga In Silico Multi-Target Approach Revealed Potential Lead Compounds as Scaffold for the Synthesis of Chemical Analogues Targeting SARS-CoV-2 Biology docking simulation SARS-CoV-2 spike protein 3CLpro COVID-19 multi-target inhibitors homology modeling |
| title | In Silico Multi-Target Approach Revealed Potential Lead Compounds as Scaffold for the Synthesis of Chemical Analogues Targeting SARS-CoV-2 |
| title_full | In Silico Multi-Target Approach Revealed Potential Lead Compounds as Scaffold for the Synthesis of Chemical Analogues Targeting SARS-CoV-2 |
| title_fullStr | In Silico Multi-Target Approach Revealed Potential Lead Compounds as Scaffold for the Synthesis of Chemical Analogues Targeting SARS-CoV-2 |
| title_full_unstemmed | In Silico Multi-Target Approach Revealed Potential Lead Compounds as Scaffold for the Synthesis of Chemical Analogues Targeting SARS-CoV-2 |
| title_short | In Silico Multi-Target Approach Revealed Potential Lead Compounds as Scaffold for the Synthesis of Chemical Analogues Targeting SARS-CoV-2 |
| title_sort | in silico multi target approach revealed potential lead compounds as scaffold for the synthesis of chemical analogues targeting sars cov 2 |
| topic | docking simulation SARS-CoV-2 spike protein 3CLpro COVID-19 multi-target inhibitors homology modeling |
| url | https://www.mdpi.com/2079-7737/11/3/465 |
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