Docking Simulations Exhibit Bortezomib and other Boron-containing Peptidomimetics as Potential Inhibitors of SARS-CoV-2 Main Protease
| Autor: | Marvin A. Soriano-Ursúa, Melvin N. Rosalez, R Vega-Valdez Iván, José Martín Santiago-Quintana, Eunice D. Farfán-García |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
inorganic chemicals
0303 health sciences Proteases Protease Bortezomib Chemistry Peptidomimetic medicine.medical_treatment 030302 biochemistry & molecular biology In vitro toxicology Protein Data Bank (RCSB PDB) Combinatorial chemistry 03 medical and health sciences Docking (molecular) medicine Binding site medicine.drug |
| Zdroj: | Current Chemical Biology. 14:279-288 |
| ISSN: | 2212-7968 |
| DOI: | 10.2174/2212796814999201102195651 |
| Popis: | Background:: Treatment of the COVID19 pandemic requires drug development. Boron- containing compounds are attractive chemical agents, some of them act as proteases inhibitors. Objective:: The present study explores the role of boronic moieties in molecules interacting on the binding site of the SARS-CoV-2 main protease. Methods:: Conventional docking procedure was applied by assaying boron-free and boron-containing compounds on the recently reported crystal structure of SARS-CoV-2 main protease (PDB code: 6LU7). The set of 150 ligands includes bortezomib and inhibitors of coronavirus proteases. Results:: Most of the tested compounds share contact with key residues and pose on the cleavage pocket. The compounds with a boron atom in their structure are often estimated to have higher affinity than boron-free analogues. Conclusion:: Interactions and the affinity of boron-containing peptidomimetics strongly suggest that boron-moieties increase affinity on the main protease, which is tested by in vitro assays. A Bis-boron-containing compound previously tested active on SARS-virus protease and bortezomib were identified as potent ligands. These advances may be relevant to drug designing, in addition to testing available boron-containing drugs in patients with COVID19 infection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|