Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2
| Autor: | Israel Cabeza de Vaca, Chun-Hui Zhang, Karen S. Anderson, Julian Tirado-Rives, Maria-Elena Liosi, Mohammad Mehdi Ghahremanpour, Joseph A. Ippolito, Maya Deshmukh, William L. Jorgensen |
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| Rok vydání: | 2020 |
| Předmět: |
Letter
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) medicine.medical_treatment protease inhibitors Context (language use) Efonidipine Pharmacology 01 natural sciences Biochemistry Article chemistry.chemical_compound Boceprevir Drug Discovery medicine chemistry.chemical_classification Virtual screening Protease drug repurposing 010405 organic chemistry SARS-CoV-2 Chemistry Organic Chemistry virtual screening 0104 chemical sciences 010404 medicinal & biomolecular chemistry Drug repositioning Enzyme Bedaquiline medicine.drug |
| Zdroj: | ACS Medicinal Chemistry Letters bioRxiv |
| Popis: | A consensus virtual screening protocol has been applied to ca. 2000 approved drugs to seek inhibitors of the main protease (Mpro) of SARS-CoV-2, the virus responsible for COVID-19. 42 drugs emerged as top candidates, and after visual analyses of the predicted structures of their complexes with Mpro, 17 were chosen for evaluation in a kinetic assay for Mpro inhibition. Remarkably 14 of the compounds at 100-μM concentration were found to reduce the enzymatic activity and 5 provided IC50 values below 40 μM: manidipine (4.8 μM), boceprevir (5.4 μM), lercanidipine (16.2 μM), bedaquiline (18.7 μM), and efonidipine (38.5 μM). Structural analyses reveal a common cloverleaf pattern for the binding of the active compounds to the P1, P1’, and P2 pockets of Mpro. Further study of the most active compounds in the context of COVID-19 therapy is warranted, while all of the active compounds may provide a foundation for lead optimization to deliver valuable chemotherapeutics to combat the pandemic. |
| Databáze: | OpenAIRE |
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