Identification of potential COVID-19 main protease inhibitors using structure-based pharmacophore approach, molecular docking and repurposing studies
The current outbreak of novel coronavirus (COVID-19) infections urges the need to identify potential therapeutic agents. Therefore, the repurposing of FDA-approved drugs against today’s diseases involves the use of de-risked compounds with potentially lower costs and shorter development timelines. I...
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| Format: | Article |
| Language: | English |
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Sciendo
2021-06-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2021-0016 |
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| author | Daoud Safa Alabed Shada J. Dahabiyeh Lina A. |
| author_facet | Daoud Safa Alabed Shada J. Dahabiyeh Lina A. |
| author_sort | Daoud Safa |
| collection | DOAJ |
| description | The current outbreak of novel coronavirus (COVID-19) infections urges the need to identify potential therapeutic agents. Therefore, the repurposing of FDA-approved drugs against today’s diseases involves the use of de-risked compounds with potentially lower costs and shorter development timelines. In this study, the recently resolved X-ray crystallographic structure of COVID-19 main protease (Mpro) was used to generate a pharmacophore model and to conduct a docking study to capture antiviral drugs as new promising COVID-19 main protease inhibitors. The developed pharmacophore successfully captured five FDA-approved antiviral drugs (lopinavir, remdesivir, ritonavir, saquinavir and raltegravir). The five drugs were successfully docked into the binding site of COVID-19 Mpro and showed several specific binding interactions that were comparable to those tying the co-crystallized inhibitor X77 inside the binding site of COVID-19 Mpro. Three of the captured drugs namely, remdesivir, lopinavir and ritonavir, were reported to have promising results in COVID-19 treatment and therefore increases the confidence in our results. Our findings suggest an additional possible mechanism of action for remdesivir as an antiviral drug inhibiting COVID-19 Mpro. Additionally, a combination of structure-based pharmacophore modeling with a docking study is expected to facilitate the discovery of novel COVID-19 Mpro inhibitors. |
| format | Article |
| id | doaj-art-b5d5569501a34e3aaf949ec61cc69077 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2021-06-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-b5d5569501a34e3aaf949ec61cc690772025-02-02T00:31:54ZengSciendoActa Pharmaceutica1846-95582021-06-0171216317410.2478/acph-2021-0016acph-2021-0016Identification of potential COVID-19 main protease inhibitors using structure-based pharmacophore approach, molecular docking and repurposing studiesDaoud Safa0Alabed Shada J.1Dahabiyeh Lina A.2Department of Pharmaceutical, Chemistry and Pharmacognosy, Faculty of Pharmacy, Applied Science, Private University, Amman, JordanDepartment of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman, JordanDepartment of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman, JordanThe current outbreak of novel coronavirus (COVID-19) infections urges the need to identify potential therapeutic agents. Therefore, the repurposing of FDA-approved drugs against today’s diseases involves the use of de-risked compounds with potentially lower costs and shorter development timelines. In this study, the recently resolved X-ray crystallographic structure of COVID-19 main protease (Mpro) was used to generate a pharmacophore model and to conduct a docking study to capture antiviral drugs as new promising COVID-19 main protease inhibitors. The developed pharmacophore successfully captured five FDA-approved antiviral drugs (lopinavir, remdesivir, ritonavir, saquinavir and raltegravir). The five drugs were successfully docked into the binding site of COVID-19 Mpro and showed several specific binding interactions that were comparable to those tying the co-crystallized inhibitor X77 inside the binding site of COVID-19 Mpro. Three of the captured drugs namely, remdesivir, lopinavir and ritonavir, were reported to have promising results in COVID-19 treatment and therefore increases the confidence in our results. Our findings suggest an additional possible mechanism of action for remdesivir as an antiviral drug inhibiting COVID-19 Mpro. Additionally, a combination of structure-based pharmacophore modeling with a docking study is expected to facilitate the discovery of novel COVID-19 Mpro inhibitors.https://doi.org/10.2478/acph-2021-0016covid-19main proteasepharmacophorestructure-based modelingdocking studyremdesivirrepurposing |
| spellingShingle | Daoud Safa Alabed Shada J. Dahabiyeh Lina A. Identification of potential COVID-19 main protease inhibitors using structure-based pharmacophore approach, molecular docking and repurposing studies Acta Pharmaceutica covid-19 main protease pharmacophore structure-based modeling docking study remdesivir repurposing |
| title | Identification of potential COVID-19 main protease inhibitors using structure-based pharmacophore approach, molecular docking and repurposing studies |
| title_full | Identification of potential COVID-19 main protease inhibitors using structure-based pharmacophore approach, molecular docking and repurposing studies |
| title_fullStr | Identification of potential COVID-19 main protease inhibitors using structure-based pharmacophore approach, molecular docking and repurposing studies |
| title_full_unstemmed | Identification of potential COVID-19 main protease inhibitors using structure-based pharmacophore approach, molecular docking and repurposing studies |
| title_short | Identification of potential COVID-19 main protease inhibitors using structure-based pharmacophore approach, molecular docking and repurposing studies |
| title_sort | identification of potential covid 19 main protease inhibitors using structure based pharmacophore approach molecular docking and repurposing studies |
| topic | covid-19 main protease pharmacophore structure-based modeling docking study remdesivir repurposing |
| url | https://doi.org/10.2478/acph-2021-0016 |
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