Repurposing of renin inhibitors as SARS-COV-2 main protease inhibitors: A computational study
| Autor: | Mohamed K El-Ashrey, Yassin M. Nissan, Rana H. Refaey |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Antagonists & inhibitors medicine.drug_class medicine.medical_treatment Pharmacology Renin inhibitor Article 03 medical and health sciences Catalytic Domain Virology Renin medicine Protease Inhibitors Coronavirus 3C Proteases 030304 developmental biology chemistry.chemical_classification 0303 health sciences Virtual screening Protease biology SARS-CoV-2 030302 biochemistry & molecular biology Drug Repositioning Imidazoles COVID-19 Active site COVID-19 Drug Treatment Drug repositioning Enzyme chemistry biology.protein Remikiren Pharmacophore Computational study Repurposing Protein Binding |
| Zdroj: | Virology |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2020.12.008 |
| Popis: | The COVID-19 pandemic has urged for the repurposing of existing drugs for rapid management and treatment. Renin inhibitors down regulation of ACE2, which is an essential receptor for SARS-CoV-2 infection that is responsible for COVID-19, in addition to their ability to act as protease inhibitors were encouraging aspects for their investigation as possible inhibitors of main protease of SARS-CoV-2 via computational studies. A Pharmacophore model was generated using the newly released SARS-COV-2 main protease inhibitors. Virtual screening was performed on renin inhibitors, and Drug likeness filter identified remikiren and 0IU as hits. Molecular docking for both compounds showed that the orally active renin inhibitor remikiren (Ro 42–5892) of Hoffmann–La Roche exhibited good molecular interaction with Cys145 and His41 in the catalytic site of SARS-CoV-2 main protease. Molecular dynamics simulation suggested that the drug is stable in the active site of the enzyme. Graphical abstract Image 1 Highlights • For rapid management of COVID-19, drug repurposing was widely carried out. • Renin inhibitors downregulate ACE2, decreasing the risk of SARS-COV-2 infection. • SARS-COV-2 main protease is a potential target for renin inhibitors. • Pharmacophore model was generated and virtually screened on renin inhibitors. • Remikiren was a hit, furtherly studied through molecular docking and dynamics. |
| Databáze: | OpenAIRE |
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