In Silico Discovery of Small-Molecule Inhibitors Targeting SARS-CoV-2 Main Protease
The COVID-19 pandemic has caused severe health threat globally, and novel SARS-Cov-2 inhibitors are urgently needed for antiviral treatment. The main protease (M<sup>pro</sup>) of the virus is one of the most effective and conserved targets for anti-SARS-CoV-2 drug development. In this s...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/14/5320 |
| _version_ | 1797588002515451904 |
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| author | Menghan Gao Dongwei Kang Na Liu Yanna Liu |
| author_facet | Menghan Gao Dongwei Kang Na Liu Yanna Liu |
| author_sort | Menghan Gao |
| collection | DOAJ |
| description | The COVID-19 pandemic has caused severe health threat globally, and novel SARS-Cov-2 inhibitors are urgently needed for antiviral treatment. The main protease (M<sup>pro</sup>) of the virus is one of the most effective and conserved targets for anti-SARS-CoV-2 drug development. In this study, we utilized a molecular docking-based virtual screening approach against the conserved catalytic site to identify small-molecule inhibitors of SARS-CoV-2 M<sup>pro</sup>. Further biological evaluation helped us identify two compounds, AF-399/40713777 and AI-942/42301830, with moderate inhibitory activity. Besides that, the in silico data, including molecular dynamics (MD) simulation, binding free energy calculations, and AMDET profiles, suggested that these two hits could serve as the starting point for the future development of COVID-19 intervention treatments. |
| first_indexed | 2024-03-11T00:47:50Z |
| format | Article |
| id | doaj.art-5475ad9c9b0242368ccfad4f2d66aa3a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T00:47:50Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-5475ad9c9b0242368ccfad4f2d66aa3a2023-11-18T20:40:22ZengMDPI AGMolecules1420-30492023-07-012814532010.3390/molecules28145320In Silico Discovery of Small-Molecule Inhibitors Targeting SARS-CoV-2 Main ProteaseMenghan Gao0Dongwei Kang1Na Liu2Yanna Liu3School of Pharmacy and Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, 6699 Qingdao Road, Jinan 250117, ChinaDepartment of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, ChinaDepartment of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, ChinaSchool of Pharmacy and Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, 6699 Qingdao Road, Jinan 250117, ChinaThe COVID-19 pandemic has caused severe health threat globally, and novel SARS-Cov-2 inhibitors are urgently needed for antiviral treatment. The main protease (M<sup>pro</sup>) of the virus is one of the most effective and conserved targets for anti-SARS-CoV-2 drug development. In this study, we utilized a molecular docking-based virtual screening approach against the conserved catalytic site to identify small-molecule inhibitors of SARS-CoV-2 M<sup>pro</sup>. Further biological evaluation helped us identify two compounds, AF-399/40713777 and AI-942/42301830, with moderate inhibitory activity. Besides that, the in silico data, including molecular dynamics (MD) simulation, binding free energy calculations, and AMDET profiles, suggested that these two hits could serve as the starting point for the future development of COVID-19 intervention treatments.https://www.mdpi.com/1420-3049/28/14/5320SARS-CoV-2main protease inhibitorsmolecular docking-based virtual screeningMD simulation |
| spellingShingle | Menghan Gao Dongwei Kang Na Liu Yanna Liu In Silico Discovery of Small-Molecule Inhibitors Targeting SARS-CoV-2 Main Protease Molecules SARS-CoV-2 main protease inhibitors molecular docking-based virtual screening MD simulation |
| title | In Silico Discovery of Small-Molecule Inhibitors Targeting SARS-CoV-2 Main Protease |
| title_full | In Silico Discovery of Small-Molecule Inhibitors Targeting SARS-CoV-2 Main Protease |
| title_fullStr | In Silico Discovery of Small-Molecule Inhibitors Targeting SARS-CoV-2 Main Protease |
| title_full_unstemmed | In Silico Discovery of Small-Molecule Inhibitors Targeting SARS-CoV-2 Main Protease |
| title_short | In Silico Discovery of Small-Molecule Inhibitors Targeting SARS-CoV-2 Main Protease |
| title_sort | in silico discovery of small molecule inhibitors targeting sars cov 2 main protease |
| topic | SARS-CoV-2 main protease inhibitors molecular docking-based virtual screening MD simulation |
| url | https://www.mdpi.com/1420-3049/28/14/5320 |
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