Identification of a repurposed drug as an inhibitor of Spike protein of human coronavirus SARS-CoV-2 by computational methods
| العنوان: | Identification of a repurposed drug as an inhibitor of Spike protein of human coronavirus SARS-CoV-2 by computational methods |
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| المؤلفون: | Sruthi Unni, Saravanamuthu Thiyagarajan, Balasundaram Padmanabhan, Snehal Aouti |
| المصدر: | Journal of Biosciences |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0106 biological sciences, Drug, Protein Conformation, media_common.quotation_subject, In silico, Pneumonia, Viral, Spike protein, Molecular Dynamics Simulation, 01 natural sciences, Antiviral Agents, Article, General Biochemistry, Genetics and Molecular Biology, PubChem, Betacoronavirus, Protein structure, Bisoxatin, Oxazines, Medicine, Humans, DrugBank, Pathogen, Pandemics, media_common, MD simulations, business.industry, SARS-CoV-2, Drug Repositioning, COVID-19, General Medicine, Virology, Drug repositioning, Docking (molecular), Laxatives, docking, Spike Glycoprotein, Coronavirus, business, Coronavirus Infections, General Agricultural and Biological Sciences, 010606 plant biology & botany |
| الوصف: | Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is an emerging new viral pathogen that causes severe respiratory disease. SARS-CoV-2 is responsible for the outbreak of COVID-19 pandemic worldwide. As there are no confirmed antiviral drugs or vaccines currently available for the treatment of COVID-19, discovering potent inhibitors or vaccines are urgently required for the benefit of humanity. The glycosylated Spike protein (S-protein) directly interacts with human angiotensin-converting enzyme 2 (ACE2) receptor through the receptor-binding domain (RBD) of S-protein. As the S-protein is exposed to the surface and is essential for entry into the host, the S-protein can be considered as a first-line therapeutic target for antiviral therapy and vaccine development. In silico screening, docking, and molecular dynamics simulation studies were performed to identify repurposing drugs using DrugBank and PubChem library against the RBD of S-protein. The study identified a laxative drug, Bisoxatin (DB09219), which is used for the treatment of constipation and preparation of the colon for surgical procedures. It binds nicely at the S-protein-ACE2 interface by making substantial π-π interactions with Tyr505 in the 'Site 1' hook region of RBD and hydrophilic interactions with Glu406, Ser494, and Thr500. Bisoxatin consistently binds to the protein throughout the 100 ns simulation. Taken together, we propose that the discovered molecule, Bisoxatin may be a promising repurposable drug molecule to develop new chemical libraries for inhibiting SARS-CoV-2 entry into the host. |
| اللغة: | English |
| تدمد: | 0973-7138 0250-5991 |
| DOI: | 10.1007/s12038-020-00102-w |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1f4b4109cc817e35835d66ebf3b345a2 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1f4b4109cc817e35835d66ebf3b345a2 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 09737138 02505991 |
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| DOI: | 10.1007/s12038-020-00102-w |