Promising terpenes as SARS-CoV-2 spike receptor-binding domain (RBD) attachment inhibitors to the human ACE2 receptor: Integrated computational approach
| العنوان: | Promising terpenes as SARS-CoV-2 spike receptor-binding domain (RBD) attachment inhibitors to the human ACE2 receptor: Integrated computational approach |
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| المؤلفون: | Alaa R. Hameed, Halah M H Al-Hasani, Muhammad Tahir ul Qamar, Guanglin Li, Ziyad Tariq Muhseen |
| المصدر: | Journal of Molecular Liquids |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Coronavirus disease 2019 (COVID-19), medicine.drug_class, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 02 engineering and technology, Computational biology, 010402 general chemistry, 01 natural sciences, Article, Terpene, Materials Chemistry, medicine, Physical and Theoretical Chemistry, Receptor, Spectroscopy, chemistry.chemical_classification, Virtual screening, SARS-CoV-2, Terpenes, COVID-19, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Atomic and Molecular Physics, and Optics, 0104 chemical sciences, Electronic, Optical and Magnetic Materials, Enzyme, Drug development, chemistry, Computer aided drug design and discovery, Antiviral drug, 0210 nano-technology |
| الوصف: | The spike protein receptor binding domain (S-RBD) is a necessary corona-viral protein for binding and entry of coronaviruses (COVs) into the host cells. Hence, it has emerged as an attractive antiviral drug target. Therefore, present study was aimed to target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-RBD with novel bioactive compounds to retrieve potential candidates that could serve as anti-coronavirus disease 2019 (COVID-19) drugs. In this paper, computational approaches were employed, especially the structure-based virtual screening followed by molecular dynamics (MD) simulation as well as binding energy analysis for the computational identification of specific terpenes from the medicinal plants, which can block SARS-CoV-2 S-RBD binding to Human angiotensin-converting enzyme 2 (H-ACE2) and can act as potent anti-COVID-19 drugs after further advancements. The screening of focused terpenes inhibitors database composed of ~1000 compounds with reported therapeutic potential resulted in the identification of three candidate compounds, NPACT01552, NPACT01557 and NPACT00631. These three compounds established conserved interactions, which were further explored through all-atom MD simulations, free energy calculations, and a residual energy contribution estimated by MM-PB(GB)SA method. All these compounds showed stable conformation and interacted well with the hot-spot residues of SARS-CoV-2 S-RBD. Conclusively, the reported SARS-CoV-2 S-RBD specific terpenes could serve as seeds for developing potent anti-COVID-19 drugs. Importantly, the experimentally tested glycyrrhizin (NPACT00631) against SARS-CoV could be used further in the fast-track drug development process to help curb COVID-19. Highlights • SARS-CoV-2 S-RBD attachment to ACE2 receptor is characterized to discover potent inhibitors. • Computational approaches identified potent inhibitors from medicinal plant's terpenes. • Selected inhibitors represent stable/strong binding with important binding-site residues. • Selected inhibitors can facilitate the development of natural therapeutic solution of COVID-19. |
| تدمد: | 0167-7322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b524587dac92c9965bb9efef2016b48 https://pubmed.ncbi.nlm.nih.gov/33041407 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....4b524587dac92c9965bb9efef2016b48 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 01677322 |
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