A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wreaked havoc all over the world. Although vaccines for the disease have recently become available and started to be administered to the population in various countries, there i...
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/12/6468 |
| _version_ | 1797486599333740544 |
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| author | Seri Jo Luca Signorile Suwon Kim Mi-Sun Kim Oscar Huertas Raúl Insa Núria Reig Dong Hae Shin |
| author_facet | Seri Jo Luca Signorile Suwon Kim Mi-Sun Kim Oscar Huertas Raúl Insa Núria Reig Dong Hae Shin |
| author_sort | Seri Jo |
| collection | DOAJ |
| description | The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wreaked havoc all over the world. Although vaccines for the disease have recently become available and started to be administered to the population in various countries, there is still a strong and urgent need for treatments to cure COVID-19. One of the safest and fastest strategies is represented by drug repurposing (DRPx). In this study, thirty compounds with known safety profiles were identified from a chemical library of Phase II-and-up compounds through a combination of SOM Biotech’s Artificial Intelligence (AI) technology, SOM<sup>AI</sup>PRO, and in silico docking calculations with third-party software. The selected compounds were then tested in vitro for inhibitory activity against SARS-CoV-2 main protease (3CLpro or Mpro). Of the thirty compounds, three (cynarine, eravacycline, and prexasertib) displayed strong inhibitory activity against SARS-CoV-2 3CLpro. VeroE6 cells infected with SARS-CoV-2 were used to find the cell protection capability of each candidate. Among the three compounds, only eravacycline showed potential antiviral activities with no significant cytotoxicity. A further study is planned for pre-clinical trials. |
| first_indexed | 2024-03-09T23:36:29Z |
| format | Article |
| id | doaj.art-da9d3d4bdf574889b79732e4f160d3f5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:36:29Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-da9d3d4bdf574889b79732e4f160d3f52023-11-23T17:01:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012312646810.3390/ijms23126468A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) InhibitorsSeri Jo0Luca Signorile1Suwon Kim2Mi-Sun Kim3Oscar Huertas4Raúl Insa5Núria Reig6Dong Hae Shin7College of Pharmacy and Graduates School of Pharmaceutical Sciences, Ewha W. University, Seoul 03760, KoreaSOM Innovation Biotech SA., Baldiri Reixac, 4, 08028 Barcelona, SpainCollege of Pharmacy and Graduates School of Pharmaceutical Sciences, Ewha W. University, Seoul 03760, KoreaCollege of Pharmacy and Graduates School of Pharmaceutical Sciences, Ewha W. University, Seoul 03760, KoreaSOM Innovation Biotech SA., Baldiri Reixac, 4, 08028 Barcelona, SpainSOM Innovation Biotech SA., Baldiri Reixac, 4, 08028 Barcelona, SpainSOM Innovation Biotech SA., Baldiri Reixac, 4, 08028 Barcelona, SpainCollege of Pharmacy and Graduates School of Pharmaceutical Sciences, Ewha W. University, Seoul 03760, KoreaThe outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wreaked havoc all over the world. Although vaccines for the disease have recently become available and started to be administered to the population in various countries, there is still a strong and urgent need for treatments to cure COVID-19. One of the safest and fastest strategies is represented by drug repurposing (DRPx). In this study, thirty compounds with known safety profiles were identified from a chemical library of Phase II-and-up compounds through a combination of SOM Biotech’s Artificial Intelligence (AI) technology, SOM<sup>AI</sup>PRO, and in silico docking calculations with third-party software. The selected compounds were then tested in vitro for inhibitory activity against SARS-CoV-2 main protease (3CLpro or Mpro). Of the thirty compounds, three (cynarine, eravacycline, and prexasertib) displayed strong inhibitory activity against SARS-CoV-2 3CLpro. VeroE6 cells infected with SARS-CoV-2 were used to find the cell protection capability of each candidate. Among the three compounds, only eravacycline showed potential antiviral activities with no significant cytotoxicity. A further study is planned for pre-clinical trials.https://www.mdpi.com/1422-0067/23/12/6468SARS-CoV-2 3CL proteasedrug repurposingantiviralfretinhibitory compounds |
| spellingShingle | Seri Jo Luca Signorile Suwon Kim Mi-Sun Kim Oscar Huertas Raúl Insa Núria Reig Dong Hae Shin A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors International Journal of Molecular Sciences SARS-CoV-2 3CL protease drug repurposing antiviral fret inhibitory compounds |
| title | A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors |
| title_full | A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors |
| title_fullStr | A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors |
| title_full_unstemmed | A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors |
| title_short | A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors |
| title_sort | study of drug repurposing to identify sars cov 2 main protease 3clpro inhibitors |
| topic | SARS-CoV-2 3CL protease drug repurposing antiviral fret inhibitory compounds |
| url | https://www.mdpi.com/1422-0067/23/12/6468 |
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