دورية أكاديمية
Shedding Light on Dark Chemical Matter: The Discovery of a SARS-CoV-2 Mpro Main Protease Inhibitor through Intensive Virtual Screening and In Vitro Evaluation
| العنوان: | Shedding Light on Dark Chemical Matter: The Discovery of a SARS-CoV-2 Mpro Main Protease Inhibitor through Intensive Virtual Screening and In Vitro Evaluation |
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| المؤلفون: | Maria Nuria Peralta-Moreno, Yago Mena, David Ortega-Alarcon, Ana Jimenez-Alesanco, Sonia Vega, Olga Abian, Adrian Velazquez-Campoy, Timothy M. Thomson, Marta Pinto, José M. Granadino-Roldán, Maria Santos Tomas, Juan J. Perez, Jaime Rubio-Martinez |
| المصدر: | International Journal of Molecular Sciences, Vol 25, Iss 11, p 6119 (2024) |
| بيانات النشر: | MDPI AG, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | SARS-CoV-2 main protease, dark chemical matter, docking, molecular dynamics, MMPB/GBSA approach, drug design, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | The development of specific antiviral therapies targeting SARS-CoV-2 remains fundamental because of the continued high incidence of COVID-19 and limited accessibility to antivirals in some countries. In this context, dark chemical matter (DCM), a set of drug-like compounds with outstanding selectivity profiles that have never shown bioactivity despite being extensively assayed, appears to be an excellent starting point for drug development. Accordingly, in this study, we performed a high-throughput screening to identify inhibitors of the SARS-CoV-2 main protease (Mpro) using DCM compounds as ligands. Multiple receptors and two different docking scoring functions were employed to identify the best molecular docking poses. The selected structures were subjected to extensive conventional and Gaussian accelerated molecular dynamics. From the results, four compounds with the best molecular behavior and binding energy were selected for experimental testing, one of which presented inhibitory activity with a Ki value of 48 ± 5 μM. Through virtual screening, we identified a significant starting point for drug development, shedding new light on DCM compounds. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/25/11/6119; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms25116119 |
| URL الوصول: | https://doaj.org/article/112df38d75b74c1394a53416a4e0597f |
| رقم الأكسشن: | edsdoj.112df38d75b74c1394a53416a4e0597f |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms25116119 |